Nanostructured zinc oxide (ZnO) materials have been intensively studied because of their potential applications in cancer therapies. However, a better comprehension of the toxicity of the flower-like ...ZnO nanostructures toward cancer cells is still needed. In this study, we investigate the cytotoxicity of a ZnO flower-like nanostructure produced at low temperature via aqueous solution in human cervical carcinoma (HeLa) cells and noncancerous cell-line murine fibroblast (L929) cells. Nanotoxicology effects were analyzed to study apoptosis and necrosis processes, reactive oxygen species production, and cellular uptake. Cells remained incubated for 24 h in concentrations of 0.1, 1.0, and 10.0 μg mL–1 ZnO nanoparticles (NPs), with the estimated rods length varying from 1.7 ± 0.4 to 2.3 ± 0.4 μm, synthesized at different times (4, 2, and 0.5 h) by an aqueous solution method. The cytotoxic response observed in noncancerous and cancer cells showed that all of the ZnO NPs synthesized by an aqueous solution exhibited enhanced toxicology effects in cancer cells. ZnO flower-nanostructures exhibited a higher cytotoxic against cancer HeLa cells, in comparison to the noncancerous cell line L929. The cytotoxic response of ZnO NPs at 0.5, 2, and 4 h in L929 cells was not statistically significant. This ability may be of clinical interest because of the effectiveness of ZnO NPs to distinguish between normal and cancer cells in cancer therapy.
Abstract To date, nearly all self-report measures of anhedonia have been developed for use with adult samples. A valid measure of anhedonia that can be used with adolescents would be useful in order ...to address key questions about the nature and course of anhedonia during adolescence. This study examined the psychometric properties of an adolescent version of a relatively new measure of social anhedonia, namely, the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS-A). The ACIPS-A was administered to a general, community-derived Spanish adolescent sample of 449 students, including 251 males (55.9%), who ranged in age from 13 to 19 years old. Other measures included the Temporal Experience of Pleasure Scale (TEPS), anhedonia subscales from the Oviedo Schizotypy Assessment Questionnaire (ESQUIZO-Q), and the General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis yielded a four-factor solution (close relationships, casual friendships and relationships, social bonding, and negative affiliation/emancipation). The total ACIPS-A showed excellent internal consistency, with ordinal alpha = 0.95. The ACIPS-A total scores were positively correlated with the TEPS-Anticipatory scores ( r = 0.44, P < 0.001) and TEPS-Consummatory scores ( r = 0.30, P < 0.001) but not with total GHQ-12 scores. The ACIPS-A total scores were negatively correlated with social anhedonia subscale scores ( r = −0.55) taken from a measure developed for use with adolescents. These results suggest that the ACIPS-A is a valid measure for use with non-clinical adolescents and is likely to prove useful for screening purposes.
•Graphene oxide exposure caused apoptotic and necrotic stages in zebrafish gill cells.•Graphene oxide induced reactive oxygen generation in zebrafish gill cells.•Gill and liver tissues suffered ...injuries after graphene oxide chronic exposure.•Zebrafish blood cells did not present DNA damages after graphene oxide exposure.
Graphene exhibits unique physical and chemical properties that facilitate its application in many fields, including electronics and biomedical areas. However, the use of graphene and its derivatives could result in accumulation in aquatic environments, and the risks posed by these compounds for organisms are not completely understood. In this study, we investigated the effects of graphene oxide (GO) on adult zebrafish (Danio rerio). Experimental fish were exposed to 2, 10 or 20mgL−1 GO, and the cytotoxicity, genotoxicity and oxidative stress were assessed. The morphology of the gills and liver tissues was also analyzed. Graphene oxide exposure led to an increase in the number of gill cells that were in early apoptotic and necrotic stages, but genotoxicity was not observed in blood cells. We also observed the generation of Reactive Oxygen Species (ROS) in gill cells. Structural analysis revealed injuries to gill tissues, including a dilated marginal channel, lamellar fusion, clubbed tips, swollen mucocytes, epithelial lifting, aneurysms, and necrosis. Liver tissues also presented lesions such as peripherally located nuclei. Furthermore, hepatocytes exhibited a non-uniform shape, picnotic nuclei, vacuole formation, cell rupture, and necrosis. Our results showed that sub-lethal doses of graphene oxide could be harmful to fish species and thus represent risks for the aquatic food chain.
The preparation of cross-linked polymeric micrometer sized particles of styrene and pentafluorostyrene functionalized at the surface with carbohydrate moieties is described. The particles were ...synthesized
via
precipitation polymerization consisting of the radical copolymerization of pentafluorostyrene, styrene and divinylbenzene. The amount of divinylbenzene is maintained constant for all the experiments whereas the proportion of the styrene and pentafluorostyrene was varied. Therefore, different fluorinated particles with high cross-linking density were obtained where the content of the active
para
-fluorine groups varies accordingly with the feed composition. Afterwards, the carbohydrate moieties were attached to the particles in two steps by the so-called thiol-
para
-fluorine "click" reaction based on the coupling of acetylated β-
d
-thioglucopyranose onto pentafluorostyrene
via
a nucleophilic substitution of
para
-fluorine, followed by the deprotection of the acetate-protected thioglucose. The obtained glycoparticles were characterized by infrared spectroscopy and contact angle measurements, which confirmed the increasing amount of the glucose moieties in the particles as the composition of the feed on pentafluorostyrene comonomer increases. The synthesized glucose-modified particles are packed into cartridges and their binding abilities with specific proteins, such as Concanavalin A, are subsequently tested. Fluorescence spectroscopy and microscopy experiments evidenced that the glycoparticles packed into the columns are able to retain specifically Concanavalin A. Other proteins such as bovine serum albumin were tested and did not interact with the particle surface.
Highly crosslinked glycoparticles able to recognize Concanavalin A lectin are obtained by a combination of precipitation polymerization and click chemistry reaction.
Graphene oxide (GO)‐based materials have been explored in biomedical applications as active engineered materials for diagnosis and therapy. Although a large number of studies have been carried out in ...the last years, aspects involving the orientation and elongation of cells on GO immobilized on polymeric nanofibers are still scarce. We investigated the interactions between skeletal muscle cells and GO immobilized on random and aligned electrospun nanofibers of poly(caprolactone) (PCL), a biocompatible and biodegradable polymer. Oxygen plasma was employed to modify the nanofiber polymer surface to enhance the interactions between the PCL fibers and GO. Scanning electron microscopy and confocal microscopy revealed the morphology and orientation of skeletal muscle cells (C2C12 cells) on random and aligned GO/PCL nanofibers. The approach employed here is useful to investigate the interaction of skeletal muscle cells with biocompatible polymer nanofibers modified with GO intended for cell scaffolds and tissue engineering.
An efficient method is described to synthesize magnetic particles based on divinylbenzene-co-pentafluorostyrene suitable for further chemical modification and incorporation of active groups, in ...particular, carbohydrates and gold nanoparticles. The magnetic hybrid particles were prepared viaseeded precipitation polymerization consisting of the radical copolymerization of pentafluorostyrene and divinylbenzene in the presence of modified magnetite nanoparticles as seeds. Magnetite nanoparticles were first prepared by a thermal decomposition process followed by their modification with the bioinspired dopamine methacrylamide to incorporate vinyl groups at the particle surface. Then, pentafluorostyrene and divinylbenzene are polymerized through the interface of the magnetite nanoparticles to form the crosslinked polymeric shell. Afterwards, carbohydrate moieties were attached to the particles by the so-called thiol-para-fluorine "click" reaction based on the coupling of acetylated beta -d-thioglucopyranose onto pentafluorostyrene vianucleophilic substitution of para-fluorine. Moreover, the fluorinated hybrid particles reacted with 1,2-ethanedithiol in order to introduce thiol groups at the surface that were used further as platforms to stabilize the nucleation and growth of gold nanoparticles. The resultant functional particles with potential interest in recognition processes and catalysis amongst others are responsive to external magnetic fields, making the particles easy to remove from the media.
•Jacalin was efficiently conjugated with gold nanoparticles.•The nanoconjugate formation is driven by an entropic process.•The nanoconjugate exhibited high affinity and specificity against K562 ...cells.
New nanobiocomposites that combine nanoparticles and biomolecules have been shown very relevant for medical applications. Recently, cancer diagnostics and treatment have benefited from the development of nanobiocomposites, in which metallic or magnetic nanoparticles are conjugated with specific biomolecules for selective cell uptake. Despite recent advances in this area, the biomedical applications of these materials are still limited by the low efficiency of functionalization, low stability, among other factors. In this study, we report the synthesis of jacalin-conjugated gold nanoparticles, a nanoconjugate with potential application in medical areas, especially for cancer diagnosis. Jacalin is a lectin protein and it was employed due to its ability to recognize the Galβ1-3GalNAc disaccharide, which is highly expressed in tumor cells. Gold nanoparticles (AuNPs) were synthesized in the presence of generation 4 polyamidoamine dendrimer (PAMAM G4) and conjugated with fluorescein isothiocyanate (FITC)-labeled jacalin. The AuNPs/jacalin nanoconjugates were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and vibrational spectroscopy (FTIR). We also performed an investigation using isothermal titration calorimetry (ITC) and fluorescence quenching measurements to understand the interactions occurring between the AuNPs and jacalin, which revealed that the nanoconjugate formation is driven by an entropic process with good affinity. Furthermore, in vitro tests revealed that the AuNPs/jacalin-FITC nanoconjugates exhibited higher affinity for leukemic K562 cells than for healthy mononuclear blood cells, which could be useful for biomedical applications, including cancer cells imaging.
► Effects of SWCNT and PAMAM nanomaterials on the C2C12 murine cell line. ► The toxicity of SWCNT and PAMAM in C2C12 cells was correlated with the charge. ► PAMAM inhibited proliferation and cell ...adhesion more pronouncedly than SWCNT. ► First nanotoxicological study with C2C12 cells and SWCNT and PAMAM nanomaterials.
Single-wall carbon nanotubes (SWCNTs) and polyamidoamine dendrimers (PAMAM) have been proposed for a variety of biomedical applications. The combination of both molecules makes this new composite nanomaterial highly functionalizable and versatile to theranostic and drug-delivery systems. However, recent toxicological studies have shown that nanomaterials such as SWCNTs and PAMAM may have high toxicity in biological environments. Aiming to elucidate such behavior, in vitro studies with different cultured cells have been conducted in the past few years. This study focuses on the effects of SWCNT–PAMAM nanomaterials and their individual components on the C2C12 murine cell line, which is a mixed population of stem and progenitor cells. The interactions between the cells and the nanomaterials were studied with different techniques usually employed in toxicological analyses. The results showed that SWCNT–PAMAM and PAMAM inhibited the proliferation and caused DNA damage of C2C12 cells. Data from flow cytometry revealed a less toxicity in C2C12 cells exposed to SWCNT compared to the other nanomaterials. The results indicated that the toxicity of SWCNT, SWCNT–PAMAM and PAMAM in C2C12 cells can be strongly correlated with the charge of the nanomaterials.
: Capecitabine is an orally available fluoropyrimidine carbamate that selectively delivers fluorouracil (5‐FU) to tissues expressing high levels of thymidine phosphorylase (TP) such as tumors. The ...drug has demonstrated efficacy in metastatic breast cancer, colorectal, and pancreatic cancer. Although these are considered safe drugs, a growing body of literature reports adverse cardiac effects. Clinical trials indicate that capecitabine has a cardiac toxicity similar to that of infused fluoropyrimidines such as 5‐FU. Here, we review cardiotoxicity in the use of fluoropyrimidines, with particular attention toward capecitabine. We also describe a severe, reversible cardiac event that occurred in a 39‐year‐old woman, with no cardiac risk factors, treated with capecitabine for advanced breast cancer. This review and our experience confirm that fluoropyrimidine cardiotoxicity is an infrequent but documented side effect. Oncology patients under treatment should be closely observed and monitored for cardiac symptoms with particular attention in case of signs or symptoms of cardiovascular complications. The implementation of cardio‐oncology interdisciplinary teams should, in the future, reduce the impact of cancer treatment–associated cardiotoxicity syndromes.
Iron and oxidative stress have a regulatory interplay. During the oxidative burst, phagocytic cells produce free radicals such as hypochlorous acid (HOCl). Nevertheless, scarce studies evaluated the ...effect of either iron deficiency anemia (IDA) or anemia of chronic disease (ACD) on phagocyte function in the elderly. The aim of the present study was to determine the oxidative burst, phagocytosis, and nitric oxide (
•
NO) and HOCl, reactive species produced by monocytes and neutrophils in elderly with ACD or IDA. Soluble transferrin receptor, serum ferritin, and soluble transferrin receptor/log ferritin (TfR-F) index determined the iron status. The study was constituted of 39 patients aged over 60 (28 women and 11 men) recruited from the Brazilian Public Health System. Oxidative burst fluorescence intensity per neutrophil in IDA group and HOCl generation in both ACD and IDA groups were found to be lower (
p
< 0.05). The percentages of neutrophils and monocytes expressing phagocytosis in ACD group were found to be higher (
p
< 0.05). There was an overproduction of
•
NO from monocytes, whereas the fundamental generation of HOCl appeared to be lower. Phagocytosis, oxidative burst, and
•
NO and HOCl production are involved in iron metabolism regulation in elderly patients with ACD and IDA.