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Electrospinning is a technology largely employed to obtain polymer fibers with different functionalities. The electrospinning of polyvinylpyrrolidone (PVP) in the presence of silica nanoparticles, and the subsequent thermal treatment of these electrospun PVP-silica fibers, allows for the manufacturing of a self-extinguishing material stable in polar solvents. However, this material lacks consistency and does not sustain any load: this strongly limits its application in many industrial fields (e.g., the aerospace sector). Herein, we used cross-linked electrospun PVP-silica blankets and TiO2 nanoparticles to coat hemp blankets, producing a multilayer material (MM) by surface charge interaction. The MM exhibited lower stiffness than the original hemp fabric but still good mechanical behavior, V0 class at the UL 94 vertical burning test, and good stretchability even after direct flame exposure. Further, burn-through and cone calorimetry tests revealed that MM is an excellent smoke suppressant and fireproof fabric, with very low total smoke release values (as low as 4.9 vs. − 33.3 m2/m2 measured for hemp) and its structure remained intact for at least − 1 min. Finally, as all the aforementioned experimental activity, though necessary and unsubstantial, is usually quite time-consuming, two Machine Learning models were developed and exploited to predict the fire performances related to the multilayer material. Despite the incomplete starting datasets, the implemented models accounted for a successful prediction of the target parameters (namely, Time to Ignition and peak of Heat Release Rate), thanks to the assistance of ChatGPT and the exploitation of made-on-purpose decision trees. [ABSTRACT FROM AUTHOR]

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease that affects both eyes, often with asymmetric severity, potentially causing major visual complications. The seasonal management of VKC can be challenging, especially when specialists with different diagnostic and therapeutic approaches need to be consulted. The aim of this expert panel was to reach a national consensus among pediatric allergologists and ophthalmologists on the diagnosis and treatment of VKC. This consensus was developed by an expert panel of 17 Italian pediatric allergologists and ophthalmologists with over a decade of experience. Ten statements on VKC diagnosis and treatment formulated after a thorough review of current literature were evaluated by the panelists. The level of agreement was quantitatively assessed using a 5-point Likert scale. Consensus was reached if ≥ 75.0% of panelists agreed to any given statement. The consensus emphasizes the importance of evaluation by multispecialty reference centers or experienced specialists for accurate diagnosis. Prompt diagnosis, especially during active phases, is crucial and should occur before corticosteroid therapy. The Bonini score from 2007 is the preferred tool for VKC assessment, although future revisions may be considered. Short cycles of topical corticosteroids should be preferred over prolonged use, even during immunomodulatory therapy. When cyclosporine fails, tacrolimus should be considered. Conclusion: This is the first consensus on the management of VKC that has gathered the expert opinions of both pediatricians and ophthalmologists. The outcome of this multidisciplinary effort provides a uniform approach to VKC diagnosis and treatment, thereby facilitating patient management across the country. What is Known: • Vernal keratoconjunctivitis (VKC) is a chronic recurrent ocular disease particularly prevalent in the pediatric population. • Despite its relevance, there is a lack of standardized approaches shared between pediatricians and ophthalmologists, leading to notable variations in clinical practice. What is New: • This expert panel, comprising 17 pediatric allergologists and ophthalmologists, has reached a national consensus to provide standardized guidance for VKC management. • The consensus emphasizes the importance of a multidisciplinary approach to managing VKC, ensuring consistent and effective patient care. [ABSTRACT FROM AUTHOR]

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/–) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/– mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers. [ABSTRACT FROM AUTHOR]

Over recent years, great attention has been paid to the role of the complement system in the pathogenesis of age-related macular degeneration (AMD). In particular, several studies have highlighted a link between AMD development and complement dysregulation, which can probably be explained as a complement cascade hyperactivation resulting from the presence of a series of risk factors such as aging; smoking; obesity; alcohol consumption; exposure to pesticides, industrial chemicals, or pollution; and other causes of oxidative stress. This hypothesis has been mainly supported by the presence of complement mediators as constituents of drusen, representing one of the earliest and most characteristic signs of retinal damage in AMD. Additionally, activated complement mediators and some complement regulators, such as vitronectin, have been found not only in the drusen and adjacent retinal areas but also in the peripheral blood of patients with AMD. Therefore, we aim to provide a review of recently studied complement factors to highlight their role in the pathogenesis of AMD and to evaluate new potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: Myopic foveoschisis (MF) is characterized by the splitting of the retinal layers in the fovea of patients with high myopia (HM). MF may progress into foveal detachment or macular hole formation with consequent loss of central vision. The aim of this study is to investigate morphological and functional changes of the macular region in myopic subjects with and without foveoschisis. Design: Observational, cross-sectional, comparative study. Methods: Forty-eight patients with HM and 24 healthy controls were evaluated by spectral domain-optical coherence tomography (SD-OCT), multifocal electroretinography (mfERG) and microperimetry (MP-1) tests to assess macular thickness, functionality and sensitivity values, respectively. The results of the diagnostic examinations were compared between three groups: HM patients with MF (N = 24), HM patients without MF (N = 24) and control group (CG) (N = 24). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). One-way analysis of variance (ANOVA) followed by Tukey's post hoc test was used to analyze differences between groups unless specified; p values < 0.05 were considered as statistically significant. Gender distribution was compared by the Chi square test. Results: The statistical analysis with one-way ANOVA followed by Tukey's post hoc test showed a significant increase in macular thickness in HM patients with MF when compared to both HM patients without MF and CG. Morphological changes were associated with functional impairment as demonstrated by the significant decrease in amplitude of the P1 wave and MP-1 sensitivity (p < 0.05), according to the anatomical landmarks. Conclusions: This study showed that the morphological changes observed in the central retina of HM patients with MF are associated with functional alterations. High-tech diagnostic tests such as SD-OCT, mfERG and MP-1 could be useful for management in complications of MF. [ABSTRACT FROM AUTHOR]

Purpose: The retina is continually exposed to free radicals from its rich blood supply, numerous mitochondria, and photons of light which strike its surface. Most pathological processes that take place in the retina, such as inflammation, cell apoptosis, or angiogenesis, can hence involve free radicals directly or indirectly.  Since inflammatory and oxidative stress pathways underlie retinal pathology, compounds that address these factors are therefore natural choices for treatment. This review article summarizes and provides commentary on curcumin's therapeutic potential use in ophthalmology with principal focus on retinal dosorders.Methods: Curcumin (diferuloylmethane) is a compound of the Indian spice turmeric (Curcuma longa) that has been found to be efficacious in preventing and treating a number of inflammatory diseases and neoplastic processes. Curcumin exerts anti-inflammatory, anti-tumor, antioxidant, and VEGF inhibition properties through modulation of numerous biochemical mediators. This makes curcumin particularly effective in retinal disorders.Results: Curcumin has found a role in slowing, and in some cases even reversing, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, proliferative vitreoretinopathy, and retinal cancers.Conclusions: However, studies on curcumin's efficacy have been limited mostly to animal studies. Moreover, the biomedical potential of curcumin is not easy to use, given its low solubility and oral bioavailability—more attention therefore has been given to nanoparticles and liposomes. [ABSTRACT FROM AUTHOR]

In a greenhouse pot experiment, lettuce plants ( Lactuca sativa L.) were grown in a Hg-contaminated sandy soil with and without inoculation with arbuscular mycorrhizal fungi (AMF) (a commercial inoculum containing infective propagules of Rhizophagus irregularis and Funneliformis mosseae) amended with different rates of a humic acid (0, 1, and 2 g kg of soil), with the objective of verifying the synergistic effects of the two soil treatments on the Hg tolerance of lettuce plants. Our results indicated that the plant biomass was significantly increased by the combined effect of AMF and humic acid treatments. Addition of humic matter to soil boosted the AMF effect on improving the nutritional plant status, enhancing the pigment content in plant leaves, and inhibiting both Hg uptake and Hg translocation from the roots to the shoots. This was attributed not only to the Hg immobilization by stable complexes with HA and with extraradical mycorrhizal mycelium in soil and root surfaces but also to an improved mineral nutrition promoted by AMF. This work indicates that the combined use of AMF and humic acids may become a useful practice in Hg-contaminated soils to reduce Hg toxicity to crops. [ABSTRACT FROM AUTHOR]

Background and Aims: Lignin of lignocellulosic residues from biomass for energy can be exploited in sustainable agriculture as plant stimulants. Lignin monomers or their microbial bioproducts are mainly responsible for the plant growth promotion exerted by humic matter in soil. The aim of this work was to verify the humic-like bioactivity of water-soluble lignin isolated from biomass for energy towards plant growth and relate the biostimulation to the lignin molecular structure. Methods: Two water-soluble lignins isolated from giant reed (AD) and miscanthus (MG) were characterized for molecular composition by H and P 1D-, C-H 2D-, DOSY-NMR spectroscopy and for conformational structure by size-exclusion chromatography. The effect of different aqueous concentrations of lignin on germination of maize seeds and growth of maize plantlets was assessed in growth-chamber experiments. Results: Both lignins showed humic-like supramolecular structures, but different conformational stability and molecular composition. Their largest bioactivity was revealed at 10 and 50 ppm of lignin organic carbon and both significantly increased length of radicles, lateral seminal roots, and coleoptiles of maize seedlings, as well as total shoot and root dry weights and root length of maize plantlets. However, differences in AD and MG bioactivity were attributed to their conformational stabilities and content of amphiphilic molecules, which may control both the adhesion to plant roots and the release of bioactive molecules upon interactions with plant-exuded organic acids. Conclusions: The humic-like bioactivity of water-soluble lignins indicated that lignocellulosic residues from energy crops may be profitably recycled in agriculture as effective plant growth promoters, thereby increasing the economic and environmental sustainability of energy production from non-food biomasses. [ABSTRACT FROM AUTHOR]

Background: In light of the growing interest for eco-compatible fertilization, tomato plant roots were treated with four different strains of microorganisms (B1-B4) capable of positively affecting plant growth. The methanolic extracts from treated roots were analysed by reverse phase ultra-high-performance liquid chromatography hyphenated with ion trap time-of-flight high-resolution mass spectrometry to compare their metabolites with that of control plants (B0). Results: We found, in both treated and control plants, several primary metabolites, such as fatty acids and coumaric acid, and other compounds associated with secondary metabolism pathways such as that of cyclopentaneoctanoic acid (CPOA) or hydroxyoctadecadienoic acid (HODE), and additional molecules which were not characterizable with the available data. A semiquantitative assessment of all metabolites became the basis for further processing the metabolic results by principal component analysis, which highlighted significant differences in the PC1 and PC2 components. The PC1 was particularly affected by the presence of arachidonic acid, myristic acid, and two unidentified metabolites. It effectively differentiated control plants from all bioeffectors treatments, and, in particular, the B4 treatment from the rest (B1-B3). The PC2 was mainly affected by palmitic acid, heptadecanoic acid, two CPOAs, one HODE and two unidentified metabolites. These metabolites successfully differentiated the B0 control from all the bioeffectors treatments, and, especially, showed a difference between B1 and B2. Conclusions: Our findings suggest that changes in secondary pathways of lipid metabolism may underlie the biostimulation exerted by the four microbial bioeffectors of this study, and that LC-MS coupled by multivariate analysis can easily fingerprint the metabolic alterations induced by bioeffectors in tomato roots.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A click reaction is reported here for the first time as a useful technique to control the conformational stability of natural organic matter (NOM) suprastructures. Click conjugates were successfully formed between a previously butynylated NOM hydrophobic fraction and a hydrophilic polyethylene glycol (PEG)-amino chain. The click products were shown by size exclusion chromatography (HPSEC) hyphenated with Orbitrap mass spectrometry (MS) in electrospray ionization (ESI) (+), while precursors were visible in ESI (−). Despite their increase in molecular weight, HPSEC elution of click conjugates occurred after that of precursors, thus showing their departure from the NOM supramolecular association. This indicates that the click-conjugated NOM molecules were varied in their hydrophilic and cationic character and lost the capacity to accommodate in the original hydrophobic suprastructures. The most abundant product had the CHON formula, a click conjugate of butanoic acid, while other products were short-chained (C-C) linear unsaturated and hydroxylated carboxylic acids. Tandem MS revealed formation of triazole rings in clicked conjugates and their two fragmentations at the ester and the C-N alkyl-aryl bonds. The behavior of NOM molecules modified by click chemistry confirms that hydrophobicity and ionic charge of humic molecules play a pivotal role in stabilizing intermolecular forces in NOM. Moreover, the versatility of the click reaction may become useful to decorate NOM molecules with a variety of substrates, in order to alter NOM conformational and chemical properties and diversify its applications in the environment. [ABSTRACT FROM AUTHOR]

We applied humeomics to a soil unextractable humin fraction (HUM1) and its derived humin (HUM2) after removal of minerals by an HF/HCl treatment. Humeomics implies progressive separation and structural characterization of molecules released from complex humin matrices as (i) unbound, (ii) weakly ester-bound, (iii) strongly ester-bound, and (iv) ether-bound. Molecular characterization of fractions was achieved by GC-MS, thermochemolysis-GC-MS, and C-CPMAS-NMR. Both weight and chromatographic yields were higher for the clay-depleted HUM2 than those for HUM1, and this increased molecular detection in HUM2. Saturated and unsaturated alkanoic, α,ω-alkanedioic, hydroxyalkanoic acids, alkanols, and hydrocarbons were found in both HUM1 and HUM2. Abundant odd-C numbered n-alkanoic acids in unbound fractions indicated accumulation of free microbial metabolites, whereas plant-derived acids remained in fractions more tightly bound to the humin matrix. Unsaturated, n-alkanedioic, and hydroxyalkanoic acids were detected after hydrolysis of complex esters. The aromatic character in humin residues progressively increased with humeomics sequential steps, while alkyl and hydroxy-alkyl compounds were reduced. Humins contained similar components as a humic acid extracted from the same soil, implying that traditional humic pools differed in supramolecular arrangement rather than in molecular composition. The humeomic approach enables the determination of the molecular composition of humic matter and may improve knowledge of the structure-activity relations of organic matter in soil. [ABSTRACT FROM AUTHOR]

PurposeTo investigate long-term retinal changes after microincision pars plana vitrectomy surgery (MIVS) for macular hole (MH) in retinitis pigmentosa (RP) patients-retrospective and observational study.MethodsThree RP patients suffering from MH were evaluated by means of best corrected visual acuity, anterior and posterior binocular examination, spectralis high-resolution optical coherence tomography, MP-1 microperimetry (MP-1), and full-field electroretinogram (ERG), before MIVS and during the 36-month follow-up. Patients underwent simultaneous MIVS and microincision cataract surgery; IOL was positioned in capsular bag. Patients were hospitalised for 2 days after the surgery. Surgical procedure was performed according the following schedule: surgical removal of crystalline lens, MIVS with 23-gauge sutureless system trocars, core vitreous body removal, peeling of the inner limiting membrane, and balanced sterile saline solution-air-micro-structured polydimethylsiloxane (PDMS) exchange. PDMS tamponade, after 6 months starting from MIVS, was removed.ResultsIn all patients visual acuity increased after vitrectomy as a consequence of complete MH closure and restoration of retinal architecture. None of the patients developed ocular hypertension, or re-opening of MH during the 3-year follow-up. MP-1 bivariate contour ellipse area was reduced in its dimensions and improved in all patients demonstrating a better fixation.ConclusionsMIVS could be an effective treatment in RP patients with MH if medical therapy is not applicable or not sufficient. Finally more studies will be needed to improve knowledge about this genetic disease. [ABSTRACT FROM AUTHOR]

Advances in water chemistry in the last decade have improved our knowledge about the genesis, composition, and structure of dissolved organic matter, and its effect on the environment. Improvements in analytical technology, for example Fourier-transform ion cyclotron (FT-ICR) mass spectrometry (MS), homo and hetero-correlated multidimensional nuclear magnetic resonance (NMR) spectroscopy, and excitation emission matrix fluorimetry (EEMF) with parallel factor (PARAFAC) analysis for UV-fluorescence spectroscopy have resulted in these advances. Improved purification methods, for example ultrafiltration and reverse osmosis, have enabled facile desalting and concentration of freshly collected DOM samples, thereby complementing the analytical process. Although its molecular weight (MW) remains undefined, DOM is described as a complex mixture of low-MW substances and larger-MW biomolecules, for example proteins, polysaccharides, and exocellular macromolecules. There is a general consensus that marine DOM originates from terrestrial and marine sources. A combination of diagenetic and microbial processes contributes to its origin, resulting in refractory organic matter which acts as carbon sink in the ocean. Ocean DOM is derived partially from humified products of plants decay dissolved in fresh water and transported to the ocean, and partially from proteinaceous and polysaccharide material from phytoplankton metabolism, which undergoes in-situ microbial processes, becoming refractory. Some of the DOM interacts with radiation and is, therefore, defined as chromophoric DOM (CDOM). CDOM is classified as terrestrial, marine, anthropogenic, or mixed, depending on its origin. Terrestrial CDOM reaches the oceans via estuaries, whereas autochthonous CDOM is formed in sea water by microbial activity; anthropogenic CDOM is a result of human activity. CDOM also affects the quality of water, by shielding it from solar radiation, and constitutes a carbon sink pool. Evidence in support of the hypothesis that part of marine DOM is of terrestrial origin, being the result of a long-term carbon sedimentation, has been obtained from several studies discussed herein. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma (PPARG) inactivation has been identified as an important step in colorectal cancer (CRC) progression, although the events involved have been partially clarified. UHRF1 is emerging as a cofactor that coordinates the epigenetic silencing of tumor suppressor genes, but its role in CRC remains elusive. Here, we report that UHRF1 negatively regulates PPARG and is associated with a higher proliferative, clonogenic and migration potential. Consistently, UHRF1 ectopic expression induces PPARG repression through its recruitment on the PPARG promoter fostering DNA methylation and histone repressive modifications. In agreement, UHRF1 knockdown elicits PPARG re-activation, accompanied by positive histone marks and DNA demethylation, corroborating its role in PPARG silencing. UHRF1 overexpression, as well as PPARG-silencing, imparts higher growth rate and phenotypic features resembling those occurring in the epithelial-mesenchymal transition. In our series of 110 sporadic CRCs, high UHRF1-expressing tumors are characterized by an undifferentiated phenotype, higher proliferation rate and poor clinical outcome only in advanced stages III-IV. In addition, the inverse relationship with PPARG found in vitro is detected in vivo and UHRF1 prognostic significance appears closely related to PPARG low expression, as remarkably validated in an independent dataset. The results demonstrate that UHRF1 regulates PPARG silencing and both genes appear to be part of a complex regulatory network. These findings suggest that the relationship between UHRF1 and PPARG may have a relevant role in CRC progression. [ABSTRACT FROM AUTHOR]

Epigenetic deregulation is involved in acute myeloid leukemia (AML) pathogenesis and epigenetic targeting drugs are in clinical trial. Since the first results with histone-deacetylase inhibitors in AML are controversial, novel single and combined treatments need to be explored. It is tempting to combine chromatin-targeting drugs. SUV39H1, the main methyl-transferase for lysine 9 tri-methylation on histone H3, interacts with oncogenes involved in AML and acts as a transcriptional repressor for hematopoietic differentiation and immortalization. We report here that pharmacological inhibition of SUV39H1 by chaetocin induces apoptosis in leukemia cell lines in vitro and primary AML cells ex vivo, and that it interferes with leukemia growth in vivo. Chaetocin treatment upregulates reactive oxygen species (ROS) production as well as the transcription of death-receptor-related genes, in a ROS-dependent manner, leading to death receptor-dependent apoptosis. In addition to its direct inhibition by chaetocin, SUV39H1 is indirectly modulated by chaetocin-induced ROS. Accordingly, chaetocin potentiates other anti-AML drugs, in a ROS-dependent manner. The decryption of a dual mechanism of action against AML involving both direct and indirect SUV39H1 modulation represents an innovative read-out for the anticancer activity of chaetocin and for its synergy with other anti-AML drugs, suggesting new therapeutic combination strategies in AML. [ABSTRACT FROM AUTHOR]

Background: Intraoperative lidocaine is widely used in controlling discomfort during cataract surgery. However, recent studies have confirmed the toxic effect of lidocaine on ganglion cells. Ropivacaine is an anesthetic recently introduced in clinical practice that couples a long anesthetic effect with a mild vasoconstrictive action. Objective: The aim of this study was an in vitro evaluation of the efficacy of ropivacaine in reducing the degenerative effects usually observed during lidocaine treatment. Methods: Ropivacaine and lidocaine toxicity has been evaluated in murine fibroblasts 3T6 by measuring percentage of cell death, cell growth inhibition, and DNA degradation. The choice of this cellular line is motivated by the presence of a complete apoptotic system that can be assimilated to the endothelium precursor cells. Results: We observed that lidocaine 0.25% decreases cell viability and causes DNA degradation in murine fibroblasts 3T6, whereas ropivacaine 0.5% does not cause any cellular or molecular degenerative effect. Conclusions: Our in vitro studies confirm that ropivacaine is less toxic than lidocaine to these cells. Therefore, in vivo studies in the anterior chamber could be useful to evaluate the effects of ropivacaine versus lidocaine in intracameral anesthesia in cataract surgery. [ABSTRACT FROM AUTHOR]

Size-fractions from a soil humic acid were separated by preparative size-exclusion chromatography (SEC), desalted, and concentrated by ultrafiltration and vacuum centrifugation without being subjected to any freeze-drying process. After having assessed the lack of formation of any multiple-charged ions by high-resolution Fourier transform ion cyclotron resonance electrospray ionization (ESI) mass spectrometry (MS), the size-fractions were used by direct infusion to compare the molecular ion distribution by both atmospheric pressure chemical ionization (APCI)- and ESI-MS in negative mode. The weight- ( Mw) and number-averaged ( Mn) molecular weight obtained by ESI-MS were invariably larger than by APCI-MS for all size-fractions, thereby indicating that ESI is more efficient than APCI to evaluate the molecular mass distribution of humic samples. No substantial difference was observed when concentration and pH of unfreeze-dried humic size-fractions were varied. The negative mode was applied to assess the effect of cone voltage from −20 to −60 V on ESI of the humic size-fractions further separated through an on-line SEC column. The resulting mass spectra and Mw and Mn values suggested that the variation of cone voltage in ESI-MS affects the ionization potential of associated humic molecules more in solution rather than their fragmentation. These findings agree with previous observations which indicated a limitation of ESI in providing consistent mass detection for a complex mixture of heterogeneous humic molecules, especially when they are aggregated by a freeze-drying process. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is considered one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemotherapy and radiotherapy. Alteration in histone deacetylase (HDAC) activity has been reported in cancer, thus encouraging the development of HDAC inhibitors, whose antitumor action has been shown in both solid and hematological malignancies. However, the molecular basis for their tumor selectivity is unknown. To find an innovative therapy for the treatment of ATCs, we studied the effects of deacetylase inhibitors on thyroid tumorigenesis models. We show that HDACs 1 and 2 are overexpressed in ATCs compared with normal cells or benign tumors and that HDAC inhibitors induce apoptosis selectively in the fully transformed thyroid cells. Our results indicate that these phenomena are mediated by a novel action of HDAC inhibitors that reduces tumor necrosis factor-related apoptosis-inducing ligand protein degradation by affecting the ubiquitin-dependent pathway. Indeed, the combined treatment with HDAC and proteasome inhibitors results in synergistic apoptosis. These results strongly encourage the preclinical application of the combination deacetylase-proteasome inhibitors for the treatment of ATC. [ABSTRACT FROM AUTHOR]

Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2) belong to the family of NAD+ (nicotinamide adenine dinucleotide-positive)-dependent class III histone deacetylases and are involved in regulating lifespan. As cancer is a disease of ageing, targeting Sirtuins is emerging as a promising antitumour strategy. Here we present Salermide (N-{3-[(2-hydroxy-naphthalen-1-ylmethylene)-amino]-phenyl}-2-phenyl-propionamide), a reverse amide with a strong in vitro inhibitory effect on Sirt1 and Sirt2. Salermide was well tolerated by mice at concentrations up to 100 μM and prompted tumour-specific cell death in a wide range of human cancer cell lines. The antitumour activity of Salermide was primarily because of a massive induction of apoptosis. This was independent of global tubulin and K16H4 acetylation, which ruled out a putative Sirt2-mediated apoptotic pathway and suggested an in vivo mechanism of action through Sirt1. Consistently with this, RNA interference-mediated knockdown of Sirt1, but not Sirt2, induced apoptosis in cancer cells. Although p53 has been reported to be a target of Sirt1, genetic p53 knockdowns showed that the Sirt1-dependent proapoptotic effect of Salermide is p53-independent. We were finally able to ascribe the apoptotic effect of Salermide to the reactivation of proapoptotic genes epigenetically repressed exclusively in cancer cells by Sirt1. Taken together, our results underline Salermide's promise as an anticancer drug and provide evidence for the molecular mechanism through which Sirt1 is involved in human tumorigenesis.Oncogene (2009) 28, 781–791; doi:10.1038/onc.2008.436; published online 8 December 2008 [ABSTRACT FROM AUTHOR]

Chromatin is a dynamic macromolecular structure epigenetically modified to regulate specific gene expression. Altered chromatin function can lead to aberrant expression of growth regulators and may, ultimately, cause cancer. That many human diseases have epigenetic etiology has stimulated the development of 'epigenetic' therapies. Inhibitors of histone deacetylases (HDACIs) induce proliferation arrest, maturation and apoptosis of cancer cells, but not normal cells, in vitro and in vivo, and are currently being tested in clinical trials. We investigated the mechanism(s) underlying this tumor selectivity. We report that HDACIs induce, in addition to p21, expression of TRAIL (Apo2L, TNFSF10) by directly activating the TNFSF10 promoter, thereby triggering tumor-selective death signaling in acute myeloid leukemia (AML) cells and the blasts of individuals with AML. RNA interference revealed that the induction of p21, TRAIL and differentiation are separable activities of HDACIs. HDACIs induced proliferation arrest, TRAIL-mediated apoptosis and suppression of AML blast clonogenicity irrespective of French-American-British (FAB) classification status, karyotype and immunophenotype. No apoptosis was seen in normal CD34+ progenitor cells. Our results identify TRAIL as a mediator of the anticancer action of HDACIs. [ABSTRACT FROM AUTHOR]

In this study, we investigated the visual performance of two aspherical intraocular lenses (IOLs), Tecnis ZCB00 and Acrysof SN60WF, by measuring high-order aberration, visual evoked potentials (VEP), retinal sensitivity, and fixation stability by MP-1 microperimetry and contrast sensitivity values. Twenty-two patients with age-related cataract were randomly allocated to either the Tecnis or the Acrysof group. All measurements were taken from patients of both groups 2 months postoperatively. Statistical analysis was performed with Student's t test, where P-values < 0.05 were considered significant. Results were not statistically significant with regard to high-order aberration, VEP, retinal sensitivity, and fixation stability. However, the contrast sensitivity values varied significantly between Tecnis ZCB00 and Acrysof SN60WF, with Tecnis ZCB00 performing better. The anterior aspherical surface design of the Tecnis IOL indicated better mesopic contrast sensitivity at mediate and high frequencies, ensuring a better quality of vision after cataract surgery. [ABSTRACT FROM AUTHOR]

Two dimensional materials beyond graphene such as MoS2 and WS2 are novel and interesting class of materials whose unique physico-chemical properties can be exploited in applications ranging from leading edge nanoelectronics to the frontiers between biomedicine and biotechnology. To unravel the potential of TMD crystals in biomedicine, control over their production through green and scalable routes in biocompatible solvents is critically important. Furthermore, considering multiple applications of eco-friendly 2D dispersions and their potential impact onto live matter, their toxicity and antimicrobial activity still remain an open issue. Herein, we focus on the current demands of 2D TMDs and produce high-quality, few-layered and defect-free MoS2 nanosheets, exfoliated and dispersed in pure water, stabilized up to three weeks. Hence, we studied the impact of this material on human cells by investigating its interactions with three cell lines: two tumoral, MCF7 (breast cancer) and U937 (leukemia), and one normal, HaCaT (epithelium). We observed novel and intriguing results, exhibiting evident cytotoxic effect induced in the tumor cell lines, absent in the normal cells in the tested conditions. The antibacterial action of MoS2 nanosheets is then investigated against a very dangerous gram negative bacterium, such as two types of Salmonellas: ATCC 14028 and wild-type Salmonella typhimurium. Additionally, concentration and layer-dependent modulation of cytotoxic effect is found both on human cells and Salmonellas. [ABSTRACT FROM AUTHOR]