Photoactivatable Pt(IV) prodrugs represent nowadays an intriguing class of potential metal-based drugs, endowed with more chemical inertness in their oxidized form and better selectivity for the target with respect to the clinically established Pt(II) compounds. In fact, they have the possibility to be reduced by light irradiation directly at the site of interest. For this reason, we synthesized a new Pt(IV) complex, [Pt(OCOCH₃)₃(4′-phenyl-2,2′:6′,2′′-terpyridine)][CF₃SO₃] (1), that is well soluble in aqueous medium and totally unreactive towards selected model biomolecules until its reduction. The highlight of this work is the rapid and efficient photoreduction of 1 with visible light (460 nm), which leads to its reactive Pt(II) analogue. This behavior was made possible by taking advantage of an efficient catalytic system based on flavin and NADH, which is naturally present in the cellular environment. As a comparison, the reduction of 1 was also studied with simple UV irradiation, but both UV-Vis spectrophotometry and ¹H-NMR spectrometry showed that the flavin-catalyzed reduction with visible light was faster. Lastly, the reactivity against two representative biological targets, i.e., human serum albumin and one monofilament oligonucleotide fragment, was evaluated by high-resolution mass spectrometry. The results clearly pointed out that the prodrug 1 did not interact with these targets until its photoreduction to the Pt(II) analogue. Full article

Antibacterial coatings on biomedical instruments are of great interest because they can suppress bacterial colonization on these instruments. In this study, antibacterial polymeric thin coatings were deposited on teflon substrates using atmospheric pressure plasma polymerization from a propane–butane mixture. The plasma polymerization was performed by means of surface dielectric barrier discharge burning in nitrogen at atmospheric pressure. The chemical composition of plasma polymerized propane–butane films was studied by energy-dispersive X-ray spectroscopy (EDX) and FTIR. The film surface properties were studied by SEM and by surface energy measurement. The EDX analysis showed that the films consisted of carbon, nitrogen and oxygen from ambient air. The FTIR analysis confirmed, in particular, the presence of alkyl, nitrile, acetylene, imide and amine groups. The deposited films were hydrophilic with a water contact angle in the range of 13–23°. The thin film deposited samples were highly active against both S. aureus and E. coli strains in general. On the other hand, the films were cytocompatible, reaching more than 80% of the cell viability threshold compared to reference polystyrene tissue. Full article

Soil salinity is one of the basic factors causing physiological, biochemical and epigenetic changes in plants. The negative effects of salt in the soil environment can be reduced by foliar application of silicon (Si). The study showed some positive effects of Si on maize plants (Zea mays L.) grown in various salinity conditions. At high soil salinity (300 and 400 mM NaCl), higher CCI content was demonstrated following the application of 0.2 and 0.3% Si. Chlorophyll fluorescence parameters (PI, F_V/F₀, F_v/F_m and RC/ABS) were higher after spraying at 0.3 and 0.4% Si, and plant gas exchange (C_i, P_N, g_s, E) was higher after spraying from 0.1 to 0.4% Si. Soil salinity determined by the level of chlorophyll a and b, and carotenoid pigments caused the accumulation of free proline in plant leaves. To detect changes in DNA methylation under salt stress and in combination with Si treatment of maize plants, the methylation-sensitive amplified polymorphism (MSAP) technique was used. The overall DNA methylation level within the 3′CCGG 5′ sequence varied among groups of plants differentially treated. Results obtained indicated alterations of DNA methylation in plants as a response to salt stress, and the effects of NaCl + Si were dose-dependent. These changes may suggest mechanisms for plant adaptation under salt stress. Full article

Biomaterial-based nanofibrous scaffolds are the most effective alternative to bone transplantation therapy. Here, two recombinant minor ampullate spidroins (spider silk proteins), R1SR2 and NR1SR2C, were blended with Poly(lactic-co-glycolic) Acid (PLGA), respectively, to generate nanofiber scaffolds by electrospinning. The N-terminal (N), C-terminal (C), repeating (R1 and R2) and spacer (S) modules were all derived from the minor ampullate spidroins (MiSp). The physical properties and structures of the blended scaffolds were measured by scanning electron microscopy (SEM), water contact angle measurement, Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), and Tensile mechanical testing. The results showed that blending of MiSp (R1SR2 and NR1SR2C) reduced the diameter of nanofibers, increased the porosity and glass transition temperatures of nanofibrous scaffolds, and effectively improved the hydrophilicity and ultimate strain of scaffolds. It is worth noting that the above changes were more significant in the presence of the N- and C-termini of MiSp. In cell culture assays, human bone mesenchymal stem cells (HBMSCs) grown on NR1SR2C/PLGA (20/80) scaffolds displayed markedly enhanced proliferative and adhesive abilities compared with counterparts grown on pure PLGA scaffolds. Jointly, these findings indicated recombinant MiSp/PLGA, particularly NR1SR2C/PLGA (20/80) blend nanofibrous scaffolds, is promising for bone tissue engineering. Full article

Moyamoya arteriopathy (MMA) is a rare cerebrovascular disorder that causes recurrent ischemic and hemorrhagic strokes, leading young patients to severe neurological deficits. The pathogenesis of MMA is still unknown. The disease onset in a wide number of pediatric cases raises the question of the role of genetic factors in the disease’s pathogenesis. In these patients, MMA’s clinical course, or progression, is largely unclear. By performing a comprehensive molecular and cellular profile in the plasma and CSF, respectively, of MMA pediatric patients, our study is aimed at assessing the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins at an early disease stage to clarify MMA pathogenesis and progression. We employed cytofluorimetric methods and immunoassays in pediatric MMA patients and matched control subjects by age and sex. We detected increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF (i.e., angiopoietin-2 and VEGF-A). This finding is probably associated with deregulated angiogenesis, as stated by the moderate severity of collateral vessel network development (Suzuki III-IV). The absence of significant modulation of neurofilament light in CSF led us to rule out the presence of substantial neuronal injury in MMA children. Despite the limited cohort of pediatric patients, we found some peculiar cellular and molecular characteristics in their blood and CSF samples. Our findings may be confirmed by wider and perspective studies to identify predictive or prognostic circulating biomarkers and potential therapeutic targets for personalized care of MMA pediatric patients. Full article

The aim of this study was to investigate the expression of miR-17∼92 cluster members in chronic lymphocytic leukemia (CLL) patients. Six microRNAs (miRNAs)—miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1—very poorly characterized in CLL patients, were chosen for the study to consider their possible role as cancer biomarkers. It is currently unclear to which extent miR-17~92 expression is related to other routinely measured CLL markers, and whether the findings can be of any clinical significance. To achieve this goal, we report the expression levels of these miRNAs detected by RT-qPCR in purified CD19+ B lymphocytes of 107 CLL patients and correlate them with existing clinical data. The study provides new evidence regarding the heterogeneity of miR-17~92 cluster members’ expression in CLL patients. Higher miR-17-5p expression was associated with unfavorable prognostic factors (i.e., 17p and 11q deletions, CD38 and ZAP-70 expression). On the other hand, miR-19a, miR-20a, and miR-92a-1 negatively correlated with these adverse factors. The presence of del(13q) as a sole aberration was associated with a significantly lower miR-17-5p as well as higher miR-19a-3p and miR-92a-1-5p expression compared to patients carrying unfavorable genetic aberrations. Particularly, miR-20a could be considered an independent favorable prognostic factor. In a multivariate analysis, high miR-20a expression remained an independent marker predicting long TTT (time to treatment) for CLL patients. Full article

Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging. Full article

Recent advances have suggested that non-coding miRNAs (such as miR-21, miR-27, miR-145, miR-155, miR-365, miR-375 and miR-494) may be involved in multiple aspects of oral cancer chemotherapeutic responsiveness. This study evaluated whether these specific miRNAs are correlated with oral cancer responsiveness to chemotherapies, including Paclitaxel, Cisplatin and Fluorouracil (5FU). Commercially available and well-characterized oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25 and CAL27) revealed differing resistance and chemosensitivity to these agents—with SCC9 and SCC25 demonstrating the most resistance to all chemotherapeutic agents. SCC9 and SCC25 were also the only cell lines that expressed miR-375, and were the only cell lines that did not express miR-27. In addition, the expression of miR-375 was associated with the upregulation of Rearranged L-myc fusion (RLF) and the downregulation of Centriolar protein B (POC1), whereas lack of miR-27 expression was associated with Nucleophosmin 1 (NPM1) expression. These data have revealed important regulatory pathways and mechanisms associated with oral cancer proliferation and resistance that must be explored in future studies of potential therapeutic interventions. Full article

Lipid-lowering drugs have been shown to have cardioprotective effects but may have hidden cardiotoxic properties. Therefore, here we aimed to investigate if chronic treatment with the novel lipid-lowering drug bempedoic acid (BA) exerts hidden cardiotoxic and/or cardioprotective effects in a rat model of acute myocardial infarction (AMI). Wistar rats were orally treated with BA or its vehicle for 28 days, anesthetized and randomized to three different groups (vehicle + ischemia/reperfusion (I/R), BA + I/R, and positive control vehicle + ischemic preconditioning (IPC)) and subjected to cardiac 30 min ischemia and 120 min reperfusion. IPC was performed by 3 × 5 min I/R cycles before ischemia. Myocardial function, area at risk, infarct size and arrhythmias were analyzed. Chronic BA pretreatment did not influence cardiac function or infarct size as compared to the vehicle group, while the positive control IPC significantly reduced the infarct size. The incidence of reperfusion-induced arrhythmias was significantly reduced by BA and IPC. This is the first demonstration that BA treatment does not show cardioprotective effect although moderately reduces the incidence of reperfusion-induced arrhythmias. Furthermore, BA does not show hidden cardiotoxic effect in rats with AMI, showing its safety in the ischemic/reperfused heart. Full article

PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3–4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAF^D19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated ¹⁵N-¹H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H₂O mixtures were more similar in the mixed solvents then they were in water. The ¹⁵N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the T_m melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAF^D19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF. Full article

Silanized glass fibers are popular reinforcements of acrylic denture base materials. To increase the number of surface hydroxyl groups and to improve interfacial adhesion between the matrix and reinforcements, acid or base treatments of glass fibers are commonly performed before the silanization. However, limited data are available on the effect of these treatments on the mechanical properties of acrylic matrix composite materials used for denture base applications. In this work, before the silanization of a woven glass fiber fabric (GF) with 3-(trimethoxysilyl) propyl methacrylate, activation pretreatments using HCl and NH₄OH aqueous solutions have been performed. To characterize the glass surface, FTIR spectroscopy was used. Specimens of cured acrylic denture base resin and composites were divided into five groups: (1) cured acrylic denture base resin-control group; (2) composite with non-silanized GF; (3) composite with silanized GF; (4) composite with NH₄OH activated and silanized GF; (5) composite with HCl activated and silanized GF. The flexural and impact properties of specimens were evaluated by means of three-point-bending tests and Charpy impact testing, respectively. The residual reactivity of the samples was analyzed using differential scanning calorimetry. The results of mechanical testing showed that acid and base pretreatments of the glass fabric had a positive effect on the flexural modulus of prepared composites but a negative effect on their impact strength. Possible interfacial adhesion mechanisms and the diffusion control of isothermal cure reactions due to vitrification have been discussed. Full article

L-cysteine S-sulfate, Cys-SSO₃H, and their derivatives play essential roles in biological chemistry and pharmaceutical synthesis, yet their intrinsic molecular properties have not been studied to date. In this contribution, the deprotonated anion [cysS-SO₃]⁻ was introduced in the gas phase by electrospray and characterized by size-selected, cryogenic, negative ion photoelectron spectroscopy. The electron affinity of the [cysS-SO₃]^• radical was determined to be 4.95 ± 0.10 eV. In combination with theoretical calculations, it was found that the most stable structure of [cysS-SO₃]⁻ (S₁) is stabilized via three intramolecular hydrogen bonds (HBs); i.e., one O−H⋯⋯N between the –COOH and –NH₂ groups, and two N−H⋯⋯O HBs between –NH₂ and –SO₃, in which the amino group serves as both HB acceptor and donor. In addition, a nearly iso-energetic conformer (S₂) with the formation of an O−H⋯⋯N−H⋯⋯O−S chain-type binding motif competes with S₁ in the source. The most reactive site of the molecule susceptible for electrophilic attacks is the linkage S atom. Theoretically predicted infrared spectra indicate that O−H and N−H stretching modes are the fingerprint region (2800 to 3600 cm⁻¹) to distinguish different isomers. The obtained information lays out a foundation to better understand the transformation and structure–reactivity correlation of Cys-SSO₃H in biologic settings. Full article

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion wound was created, and wound closure was monitored. Neutrophil and platelet recruitment was assessed by immunofluorescence microscopy. Mice fed the high-fat/sucrose diet-only had greater adiposity (p < 0.005) than normal diet-only fed mice; diet reversal markedly reduced adiposity. Following corneal abrasion, wound closure was delayed by ~6 h (p ≤ 0.01) and, at 30 h post-wounding, fewer neutrophils reached the wound center and fewer extravascular platelets were present at the limbus (p < 0.05). Diet restored normal wound closure and neutrophil and platelet influx in the injured cornea. These data suggest compositional changes to the diet may be an effective diet-based therapeutic strategy for maintaining or restoring corneal health. Full article

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients. Full article

The PRDM family of methyltransferases has been implicated in cellular proliferation and differentiation and is deregulated in human diseases, most notably in cancer. PRDMs are related to the SET domain family of methyltransferases; however, from the 19 PRDMs only a few PRDMs with defined enzymatic activities are known. PRDM15 is an uncharacterized transcriptional regulator, with significant structural disorder and lack of defined small-molecule binding pockets. Many aspects of PRDM15 are yet unknown, including its structure, substrates, reaction mechanism, and its methylation profile. Here, we employ a series of computational approaches for an exploratory investigation of its potential substrates and reaction mechanism. Using the knowledge of PRDM9 and current knowledge of PRDM15 as basis, we tried to identify genuine substrates of PRDM15. We start from histone-based peptides and learn that the native substrates of PRDM15 may be non-histone proteins. In the future, a combination of sequence-based approaches and signature motif analysis may provide new leads. In summary, our results provide new information about the uncharacterized methyltransferase, PRDM15. Full article