Aim: Today, there is a lack of research studies concerning human acute exposure to nanoparticles (NPs). Our investigation aimed to simulate real-world acute inhalation exposure to NPs released during work with dental nanocomposites in a dental office or technician laboratory. Methods: Blood samples from female volunteers were processed before and after inhalation exposure. Transcriptomic mRNA and miRNA expression changes were analyzed. Results: We detected large interindividual variability, 90 significantly deregulated mRNAs, and 4 miRNAs when samples of participants before and after dental nanocomposite grinding were compared. Conclusion: The results suggest that inhaled dental NPs may present an occupational hazard to human health, as indicated by the changes in the processes related to oxidative stress, synthesis of eicosanoids, and cell division.
What is this article about? We searched for a possible impact of acute inhalation exposure to nanoparticles (NPs) released during the grinding of dental nanocomposites used for teeth reconstruction. The exposure design utilized in our study simulated the acute exposure of the dental staff to the NPs. Our research fills the gaps in knowledge in the field of acute human inhalation exposure to dental nanocomposites.What were the results? Results indicate that the impact of exposure to NPs is dependent on the style of working as well as on the interindividual biological variability among study subjects. Changes in expression levels of genes associated with an increase of oxidative stress, synthesis of eicosanoids (signaling molecules related to e.g., immune responses), and cell division were detected.What do the results of the study mean? All the observed changes may contribute to the pathogenesis of neurodegenerative disorders, carcinogenesis, or problems during pregnancy. Occupational exposure to inhaled NPs, including those generated in dental practice can pose a significant health risk, and protective measures when working with these materials should be considered. More research is needed to compare our results with chronic (long-term) exposure to similar materials to show the hazards related to their inhalation.
- Klíčová slova
- acute exposure, nanocomposite, nanoparticles, stomatology, transcriptomics,
- MeSH
- dospělí MeSH
- inhalační expozice * škodlivé účinky MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mikro RNA * genetika MeSH
- nanočástice chemie MeSH
- nanokompozity * chemie MeSH
- oxidační stres účinky léků MeSH
- pracovní expozice škodlivé účinky MeSH
- transkriptom * účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- messenger RNA MeSH
- mikro RNA * MeSH
Aim: To find a practical biomonitoring method for researchers exposed to nanoparticles causing oxidative stress. Methods: In a continuation of a study in 2016-2018, biological samples (plasma, urine and exhaled breath condensate [EBC]) were collected in 2019-2020 from 43 researchers (13.8 ± 3.0 years of exposure) and 45 controls. Antioxidant status was assessed using glutathione (GSH) and ferric-reducing antioxidant power, while oxidative stress was measured as thiobarbituric acid reactive substances, all using spectrophotometric methods. Researchers' personal nanoparticle exposure was monitored. Results: Plasma GSH was elevated in researchers both before and after exposure (p < 0.01); postexposure plasma GSH correlated with nanoparticle exposure, and GSH in EBC increased. Conclusion: The results suggest adaptation to chronic exposure to nanoparticles, as monitored by plasma and EBC GSH.
What is this study about? Identifying markers of oxidative stress and/or adaptation to oxidation stress could offer tools for monitoring exposure to nanoparticles in exposed researchers. In this study, we question whether these markers correlate with their personal exposure during the shift. What were the results? We found that exposure to nanoparticles correlated with the antioxidant marker glutathione, which is higher in workers who are already pre-exposed. What do the results mean? This study suggests that the researchers have adapted to nanoparticle exposure and are ready to combat oxidative stress. However, the similarity with increased markers of oxidative stress from asbestos and silica exposure, including nucleic acid oxidation, previously found in these researchers highlights the need for further research in this area to better understand and prevent potential future effects.
- Klíčová slova
- adaptation, antioxidant status, inhalation, nanoparticles, occupational, oxidative stress,
- MeSH
- antioxidancia * MeSH
- biologické markery metabolismus MeSH
- dechové testy metody MeSH
- glutathion MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
- nanočástice * MeSH
- oxidační stres MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia * MeSH
- biologické markery MeSH
- glutathion MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
Background: Exosomes are extracellular vesicles with the ability to encapsulate bioactive molecules, such as therapeutics. This study identified a new exosome mediated route of doxorubicin and poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA)-bound doxorubicin trafficking in the tumor mass. Materials & methods: Exosome loading was achieved via incubation of the therapeutics with an adherent human breast adenocarcinoma cell line and its derived spheroids. Exosomes were characterized using HPLC, nanoparticle tracking analysis (NTA) and western blotting. Results: The therapeutics were successfully loaded into exosomes. Spheroids secreted significantly more exosomes than adherent cells and showed decreased viability after treatment with therapeutic-loaded exosomes, which confirmed successful transmission. Conclusion: To the best of our knowledge, this study provides the first evidence of pHPMA-drug conjugate secretion by extracellular vesicles.
Background: In cancer treatment, low-molecular-weight drugs (e.g., doxorubicin [DOX]) with a broad spectrum of side effects are commonly used. Through their conjugation with hydrophilic polymers – N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers – for example, most of the side effects can be reduced. These drug–polymer conjugates are delivered via bloodstream into the tumor. This study aimed to identify a new exosome-mediated route of DOX and polyHPMA(pHPMA)–DOX conjugates trafficking inside the tumor mass. Exosomes are small lipid membrane vesicles constitutively released from most of the cell types, including the tumor cells. Exosomes are able to encapsulate low-molecular-weight drugs. Methods: Exosomes were loaded with DOX and pHPMA-DOX in vitro via coincubation with cancer cells. Exosomes were isolated from the conditioned-cultivation medium after their release from cells and characterized (size, numbers, protein marker profiles). Results: The therapeutics were successfully loaded into exosomes and transmitted to the tumor cells. To the best of our knowledge, this is the first evidence of the pHPMA–drug conjugate secretion by exosomes.
- Klíčová slova
- cytotoxicity, drug delivery, extracellular vesicles, polymer, tumor,
- MeSH
- adenokarcinom * farmakoterapie MeSH
- doxorubicin farmakologie terapeutické užití MeSH
- exozómy * MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- polymery MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- doxorubicin MeSH
- polymery MeSH
Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600-800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.
- Klíčová slova
- dermal infections, dermal safety, nanomedicine, nanoparticle-based intervention, submicronization,
- MeSH
- antibakteriální látky chemie MeSH
- antiinfekční látky * farmakologie MeSH
- chlorochinolinoly * MeSH
- mikrobiální testy citlivosti MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- antiinfekční látky * MeSH
- chlorochinolinoly * MeSH
- chloroxine MeSH Prohlížeč
- MeSH
- biomimetika * MeSH
- lékové transportní systémy MeSH
- nosiče léků * MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- úvodníky MeSH
- Názvy látek
- nosiče léků * MeSH
Aim: Fabrication of nanopepper (NP) for antibacterial application and elucidation of its molecular and cellular biocompatibility. Materials & methods: Synthesis of NP was achieved using a high-energy ball milling method. Following characterization, its antibacterial activity and cellular and molecular biocompatibility were evaluated in vitro by experimental and computational approaches. Results: A total of 15 h of milling pepper produced NP with a size of 44 ± 12 nm and zeta potential of -22 ± 12 mV. Bulk pepper and NP showed antibacterial activity and an LC50 of 1.9 μM and 2.1 μM in HCT116 colon cells. Components of pepper, piperine and β-caryophyllene were found to interact with superoxide dismutase [Cu-Zn] and apoptotic protease-activating factor-1-caspase-9 through different amino acids via H-bonds. Conclusion: NP exhibits significant antibacterial activity with cellular biocompatibility due to intrinsic atomic interaction. Aim: Fabrication of nanopepper (NP) for antibacterial application and elucidation of its molecular and cellular biocompatibility. Materials & methods: Synthesis of NP was achieved using a high-energy ball milling method. Following characterization, its antibacterial activity and cellular and molecular biocompatibility were evaluated in vitro by experimental and computational approaches. Results: A total of 15 h of milling pepper produced NP with a size of 44 ± 12 nm and zeta potential of -22 ± 12 mV. Bulk pepper and NP showed antibacterial activity and an LC50 of 1.9 μM and 2.1 μM in HCT116 colon cells. Components of pepper, piperine and β-caryophyllene were found to interact with superoxide dismutase [Cu-Zn] and apoptotic protease-activating factor-1-caspase-9 through different amino acids via H-bonds. Conclusion: NP exhibits significant antibacterial activity with cellular biocompatibility due to intrinsic atomic interaction.
- Klíčová slova
- HCT116 cells, Sod1, antibacterial, black pepper, caspase, cytotoxicity, piperine,
- MeSH
- antibakteriální látky farmakologie MeSH
- antiinfekční látky * MeSH
- HCT116 buňky MeSH
- lidé MeSH
- Piper nigrum * MeSH
- superoxiddismutasa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- antiinfekční látky * MeSH
- superoxiddismutasa MeSH
Aim: To evaluate the impact of a nanostructured surface created on β-titanium alloy, Ti-36Nb-6Ta, on the growth and differentiation of human mesenchymal stem cells. Materials & methods: The nanotubes, with average diameters 18, 36 and 46 nm, were prepared by anodic oxidation. Morphology, hydrophilicity and mechanical properties of the nanotube layers were characterized. The biocompatibility and osteogenic potential of the nanostructured surfaces were established using various in vitro assays, scanning electron microscopy and confocal microscopy. Results: The nanotubes lowered elastic modulus close to that of bone, positively influenced cell adhesion, improved ALP activity, synthesis of type I collagen and osteocalcin expression, but diminished early cell proliferation. Conclusion: Nanostructured Ti-36Nb-6Ta with nanotube diameters 36 nm was the most promising material for bone implantation.
- Klíčová slova
- adhesion, anodization, beta titanium alloy, biocompatibility, hMSC, mechanical properties, nanotubes, osteogenic differentiation, proliferation,
- MeSH
- buněčná adheze MeSH
- lidé MeSH
- mikroskopie elektronová rastrovací MeSH
- nanotrubičky * MeSH
- osteoblasty MeSH
- osteogeneze MeSH
- povrchové vlastnosti MeSH
- proliferace buněk MeSH
- slitiny MeSH
- titan * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- slitiny MeSH
- titan * MeSH
Aim: We aimed to develop nanoemulsions containing phosphodiesterase 4 inhibitor rolipram with different droplet sizes, to evaluate the anti-inflammatory effect against activated neutrophils and a related lung injury. Materials & methods: We prepared nanoemulsions of three different sizes, 68, 133 and 188 nm. Results: The nanoemulsion inhibited the superoxide anion but not elastase release in primary human neutrophils. The large-sized nanoemulsions were mostly internalized by neutrophils, resulting in the reduction of intracellular Ca2+ half-life. The peripheral organ distribution of near-infrared dye-tagged nanoemulsions increased, following the decrease in droplet diameter. Rolipram entrapment into intravenous nanoemulsions ameliorated pulmonary inflammation. The smallest droplet size showed improvement, compared with the largest size. Conclusion: We established a foundation for the development of nanoemulsions against inflamed lung disease.
- Klíčová slova
- anti-inflammation, lung injury, nanoemulsion, neutrophil, rolipram, size effect,
- MeSH
- antiflogistika * farmakologie MeSH
- emulze MeSH
- lidé MeSH
- nanomedicína MeSH
- neutrofily účinky léků MeSH
- zánět * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika * MeSH
- emulze MeSH
AIM: To synthesize magnetic nanoparticles loaded with the SGLT2-inhibitor canagliflozin (CANA) and evaluate its anticancer potential under normoxic and hypoxic conditions in combination or not with radiotherapy. MATERIAL & METHODS: Iron oxide nanoparticles were synthesized via an alkaline hydrolytic precipitation of iron precursor in the presence of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate). CANA was conjugated to the nanoparticles using N-ethyl-N'-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide chemistry. The anticancer efficacy of the nanoparticles was evaluated in cancer cell lines and in a mouse PDV C57 tumor model. RESULTS: In the mouse xenograft cancer model, the combination of CANA-loaded nanoparticles with radiotherapy (in the presence of an external magnetic field at the tumor site) exhibited higher antitumor activity compared with the combination of free CANA with radiotherapy. CONCLUSION: The results obtained indicate the potential that the combination of selective delivery of a SGLT2 inhibitor such as CANA with radiotherapy holds as an anticancer treatment.
- Klíčová slova
- canagliflozin, hypoxia, magnetic nanoparticles,
- MeSH
- canagliflozin chemie farmakologie MeSH
- glifloziny chemie farmakologie MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- magnetické nanočástice aplikace a dávkování chemie MeSH
- myši MeSH
- nádorová hypoxie účinky léků MeSH
- nádory farmakoterapie genetika radioterapie MeSH
- transportér 2 pro sodík a glukózu účinky léků MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- železité sloučeniny chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- canagliflozin MeSH
- ferric oxide MeSH Prohlížeč
- glifloziny MeSH
- magnetické nanočástice MeSH
- SLC5A2 protein, human MeSH Prohlížeč
- transportér 2 pro sodík a glukózu MeSH
- železité sloučeniny MeSH
- Klíčová slova
- nanoparticles, rifampicin, tuberculosis,
- Publikační typ
- časopisecké články MeSH
