INTRODUCTION AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the nasal cavity, penetrates the nasal epithelial cells through the interaction of its spike protein with the host cell receptor angiotensin-converting enzyme 2 (ACE2) and then triggers a cytokine storm. We aimed to assess the biocompatibility of fullerenol nanoparticles C60(OH)40 and ectoine, and to document their effect on the protection of primary human nasal epithelial cells (HNEpCs) against the effects of interaction with the fragment of virus - spike protein. This preliminary research is the first step towards the construction of a intranasal medical device with a protective, mechanical function against SARS-CoV-2 similar to that of personal protective equipment (eg masks). METHODS: We used HNEpCs and the full-length spike protein from SARS-CoV-2 to mimic the first stage of virus infection. We assessed cell viability with the XTT assay and a spectrophotometer. May-Grünwald Giemsa and periodic acid-Schiff staining served to evaluate HNEpC morphology. We assessed reactive oxygen species (ROS) production by using 2',7'-dichlorofluorescin diacetate and commercial kit. Finally, we employed reverse transcription polymerase chain reaction, Western blotting and confocal microscopy to determine the expression of angiotensin-converting enzyme 2 (ACE2) and inflammatory cytokines. RESULTS: There was normal morphology and unchanged viability of HNEpCs after incubation with 10 mg/L C60(OH)40, 0.2% ectoine or their composite for 24 h. The spike protein exerted cytotoxicity via ROS production. Preincubation with the composite protected HNEpCs against the interaction between the spike protein and the host membrane and prevented the production of key cytokines characteristic of severe coronavirus disease 2019, including interleukin 6 and 8, monocyte chemotactic protein 1 and 2, tissue inhibitor of metalloproteinases 2 and macrophage colony-stimulating factor. CONCLUSION: In the future, the combination of fullerenol and ectoine may be used to prevent viral infections as an intranasal medical device for people with reduced immunity and damaged mucous membrane.
- MeSH
- aminokyseliny diaminové MeSH
- angiotensin konvertující enzym 2 metabolismus MeSH
- COVID-19 * prevence a kontrola MeSH
- cytokiny metabolismus MeSH
- epitelové buňky * účinky léků virologie MeSH
- fullereny * farmakologie chemie MeSH
- glykoprotein S, koronavirus * metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- nanočástice * chemie MeSH
- nosní sliznice účinky léků cytologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- SARS-CoV-2 * účinky léků MeSH
- syndrom uvolnění cytokinů * prevence a kontrola MeSH
- viabilita buněk * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Plants are subjected to a variety of abiotic stressors, including drought stress, that are fatal to their growth and ability to produce under natural conditions. Therefore, the present study was intended to investigate the drought tolerance potential of faba bean (Vicia faba L.) plants under the co-application of biochar and rhizobacteria, Cellulomonas pakistanensis (National Culture Collection of Pakistan (NCCP)11) and Sphingobacterium pakistanensis (NCCP246). The experiment was initiated by sowing the inoculated seeds with the aforementioned rhizobacterial strains in earthen pots filled with 3 kg of sand-mixed soil and 5% biochar. The morphology of biochar was observed with highly porous nature, along with the detection of various essential elements. The biochemical and physiological data showed that phenolic compounds and osmolytes were adversely affected by the induction of drought stress. However, the application of biochar and rhizobacteria boosted the level of flavonoids on average by 52.03%, total phenols by 50.67%, soluble sugar by 82.85%, proline by 76.81%, glycine betaine by 107.25%, and total protein contents by 89.18% in all co-treatments of biochar and rhizobacteria. In addition, stress indicator compounds, including malondialdehyde (MDA) contents and H2O2, were remarkably alleviated by 54.21% and 47.03%, respectively. Similarly, the amplitude of antioxidant enzymes including catalase, peroxidase, superoxide dismutase, ascorbate peroxidase, and guaiacol peroxidase was also enhanced by 63.80%, 80.95%, 37.87%, and 58.20%, respectively, in all co-treatments of rhizobacteria and biochar. Conclusively, biochar and rhizobacteria have a magnificent role in enhancing the drought tolerance potential of crop plants by boosting the physio-biochemical traits and enhancing the level of antioxidant enzymes.
- MeSH
- antioxidancia metabolismus MeSH
- dřevěné a živočišné uhlí * chemie MeSH
- fenoly metabolismus MeSH
- flavonoidy metabolismus analýza MeSH
- fyziologický stres * MeSH
- kořeny rostlin mikrobiologie růst a vývoj MeSH
- malondialdehyd metabolismus MeSH
- období sucha * MeSH
- půdní mikrobiologie MeSH
- Vicia faba * mikrobiologie růst a vývoj MeSH
- Publikační typ
- časopisecké články MeSH
This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making.
- MeSH
- biosenzitivní techniky * přístrojové vybavení metody MeSH
- COVID-19 * diagnóza virologie MeSH
- design vybavení MeSH
- elektronické tranzistory MeSH
- fosfoproteiny MeSH
- grafit * chemie MeSH
- koronavirové nukleokapsidové proteiny izolace a purifikace MeSH
- lidé MeSH
- limita detekce MeSH
- nazofarynx virologie MeSH
- RNA virová * izolace a purifikace analýza MeSH
- SARS-CoV-2 * izolace a purifikace genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Justinian plague and its subsequent outbreaks were major events influencing Early Medieval Europe. One of the affected communities was the population of Saint-Doulchard in France, where plague victim burials were concentrated in a cemetery enclosure ditch. This study aimed to obtain more information about their life-histories using the tools of isotope analysis. MATERIALS AND METHODS: Dietary analysis using carbon and nitrogen isotopes was conducted on 97 individuals buried at Le Pressoir in Saint-Doulchard, with 36 of those originating from the enclosure ditch. This sample set includes all individuals analyzed for plague DNA in a previous study. Mobility analysis using strontium isotope analysis supplements the dietary study, with 47 analyzed humans. The results are supported by a reference sample set of 31 animal specimens for dietary analysis and 9 for mobility analysis. RESULTS: The dietary analysis results showed significantly different dietary behavior in individuals from the ditch burials, with better access to higher quality foods richer in animal protein. 87Sr/86Sr ratios are similar for both studied groups and indicate a shared or similar area of origin. DISCUSSION: The results suggest that the ditch burials contain an urban population from the nearby city of Bourges, which overall had a better diet than the rural population from Saint-Doulchard. It is implied that city's population might have been subjected to high mortality rates during the plague outbreak(s), which led to their interment in nearby rural cemeteries.
- MeSH
- dějiny středověku MeSH
- dieta * škodlivé účinky dějiny MeSH
- dítě MeSH
- dospělí MeSH
- hřbitovy MeSH
- izotopy dusíku * analýza MeSH
- izotopy stroncia analýza MeSH
- izotopy uhlíku * analýza MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mor * dějiny epidemiologie mortalita MeSH
- předškolní dítě MeSH
- zvířata MeSH
- Check Tag
- dějiny středověku MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Francie MeSH
Environmental compartments polluted with animal charcoal from the skin and hide cottage industries are rich in toxic heavy metals and diverse hydrocarbon classes, some of which are carcinogenic, mutagenic, and genotoxic, and thus require a bio-based eco-benign decommission strategies. A shotgun metagenomic approach was used to decipher the microbiome, hydrocarbon degradation genes, and heavy metal resistome of a microbial consortium (FN8) from an animal-charcoal polluted site enriched with fluorene. Structurally, the FN8 microbial consortium consists of 26 phyla, 53 classes, 119 orders, 245 families, 620 genera, and 1021 species. The dominant phylum, class, order, family, genus, and species in the consortium are Proteobacteria (51.37%), Gammaproteobacteria (39.01%), Bacillales (18.09%), Microbulbiferaceae (11.65%), Microbulbifer (12.21%), and Microbulbifer sp. A4B17 (19.65%), respectively. The microbial consortium degraded 57.56% (28.78 mg/L) and 87.14% (43.57 mg/L) of the initial fluorene concentration in 14 and 21 days. Functional annotation of the protein sequences (ORFs) of the FN8 metagenome using the KEGG GhostKOALA, KofamKOALA, NCBI's conserved domain database, and BacMet revealed the detection of hydrocarbon degradation genes for benzoate, aminobenzoate, polycyclic aromatic hydrocarbons (PAHs), chlorocyclohexane/chlorobenzene, chloroalkane/chloroalkene, toluene, xylene, styrene, naphthalene, nitrotoluene, and several others. The annotation also revealed putative genes for the transport, uptake, efflux, and regulation of heavy metals such as arsenic, cadmium, chromium, mercury, nickel, copper, zinc, and several others. Findings from this study have established that members of the FN8 consortium are well-adapted and imbued with requisite gene sets and could be a potential bioresource for on-site depuration of animal charcoal polluted sites.
- MeSH
- biodegradace MeSH
- dřevěné a živočišné uhlí MeSH
- fluoreny MeSH
- Gammaproteobacteria * MeSH
- látky znečišťující půdu * analýza MeSH
- lidé MeSH
- mikrobiota * genetika MeSH
- polycyklické aromatické uhlovodíky * metabolismus MeSH
- půda MeSH
- půdní mikrobiologie MeSH
- těžké kovy * MeSH
- uhlovodíky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Metals are widely utilized as implant materials for bone fixtures as well as stents. Biodegradable versions of these implants are highly desirable since patients do not have to undergo a second surgery for the materials to be removed. Attractive options for such materials are zinc silver alloys since they also offer the benefit of being antibacterial. However, it is important to investigate the effect of the degradation products of such alloys on the surrounding cells, taking into account silver cytotoxicity. Here we investigated zinc alloyed with 1 % of silver (Zn1Ag) and how differently concentrated extracts (1 %-100 %) of this material impact human umbilical vein endothelial cells (HUVECs). More specifically, we focused on free radical generation and oxidative stress as well as the impact on cell viability. To determine free radical production we used diamond-based quantum sensing as well as conventional fluorescent assays. The viability was assessed by observing cell morphology and the metabolic activity via the MTT assay. We found that 1 % and 10 % extracts are well tolerated by the cells. However, at higher extract concentrations we observed severe impact on cell viability and oxidative stress. We were also able to show that quantum sensing was able to detect significant free radical generation even at the lowest tested concentrations.
- MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) * účinky léků MeSH
- lidé MeSH
- nanodiamanty * chemie MeSH
- oxidační stres * účinky léků MeSH
- slitiny * chemie MeSH
- stříbro toxicita chemie MeSH
- testování materiálů metody MeSH
- viabilita buněk * účinky léků MeSH
- volné radikály metabolismus MeSH
- vstřebatelné implantáty škodlivé účinky MeSH
- zinek * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.
- MeSH
- dospělí MeSH
- glioblastom * diagnostické zobrazování terapie diagnóza radioterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- methionin * MeSH
- nádory mozku * diagnostické zobrazování terapie radioterapie diagnóza MeSH
- PET/CT metody MeSH
- plánování radioterapie pomocí počítače metody MeSH
- progrese nemoci * MeSH
- prospektivní studie MeSH
- radiofarmaka terapeutické užití MeSH
- radioizotopy uhlíku MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
In recent years, multifunctional nanocarriers that provide simultaneous drug delivery and imaging have attracted enormous attention, especially in cancer treatment. In this research, a biocompatible fluorescent multifunctional nanocarrier is designed for the co-delivery of capsaicin (CPS) and nitrogen-doped graphene quantum dots (N-GQDs) using the pH sensitive amphiphilic block copolymer (poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone), PEtOx-b-PCL). The effects of the critical formulation parameters (the amount of copolymer, the concentration of poly(vinyl alcohol) (PVA) as a stabilizing agent in the inner aqueous phase, and volume of the inner phase) are evaluated to achieve optimal nanoparticle (NP) properties using Central Composite Design. The optimized NPs demonstrated a desirable size distribution (167.8 ± 1.4 nm) with a negative surface charge (-19.9 ± 0.4) and a suitable loading capacity for CPS (70.80 ± 0.05%). The CPS & N-GQD NPs are found to have remarkable toxicity on human breast adenocarcinoma cell line (MCF-7). The solid fluorescent signal is acquired from cells containing multifunctional NPs, according to the confocal microscope imaging results, confirming the significant cellular uptake. This research illustrates the enormous potential for cellular imaging and enhanced cancer therapy offered by multifunctional nanocarriers that combine drug substances with the novel fluorescent agents.
- MeSH
- antitumorózní látky * farmakologie chemie MeSH
- dusík * chemie MeSH
- fluorescenční barviva chemie MeSH
- grafit * chemie MeSH
- kapsaicin * chemie farmakologie MeSH
- kvantové tečky * chemie terapeutické užití MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- teranostická nanomedicína * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Polyhydroxyalkanoates (PHAs) are intracellular biopolymers that microorganisms use for energy and carbon storage. They are mechanically similar to petrochemical plastics when chemically extracted, but are completely biodegradable. While they have potential as a replacement for petrochemical plastics, their high production cost using traditional carbon sources remains a significant challenge. One potential solution is to modify heterotrophic PHA-producing strains to utilize alternative carbon sources. An alternative approach is to utilize methylotrophic or autotrophic strains. This article provides an overview of bacterial strains employed for PHA production, with a particular focus on those exhibiting the highest PHA content in dry cell mass. The strains are organized according to their carbon source utilization, encompassing autotrophy (utilizing CO2, CO) and methylotrophy (utilizing reduced single-carbon substrates) to heterotrophy (utilizing more traditional and alternative substrates).
- MeSH
- Bacteria * metabolismus MeSH
- polyhydroxyalkanoáty * biosyntéza metabolismus MeSH
- uhlík metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
An ever-growing body of literature evidences the protective role of polyhydroxyalkanoates (PHAs) against a plethora of mostly physical stressors in prokaryotic cells. To date, most of the research done involved bacterial strains isolated from habitats not considered to be life-challenging or extremely impacted by abiotic environmental factors. Polar region microorganisms experience a multitude of damaging factors in combinations rarely seen in other of Earth's environments. Therefore, the main objective of this investigation was to examine the role of PHAs in the adaptation of psychrophilic, Arctic-derived bacteria to stress conditions. Arctic PHA producers: Acidovorax sp. A1169 and Collimonas sp. A2191, were chosen and their genes involved in PHB metabolism were deactivated making them unable to accumulate PHAs (ΔphaC) or to utilize them (Δi-phaZ) as a carbon source. Varying stressors were applied to the wild-type and the prepared mutant strains and their survival rates were assessed based on CFU count. Wild-type strains with a functional PHA metabolism were best suited to survive the freeze-thaw cycle - a common feature of polar region habitats. However, the majority of stresses were best survived by the ΔphaC mutants, suggesting that the biochemical imbalance caused by the lack of PHAs induced a permanent cell-wide stress response thus causing them to better withstand the stressor application. Δi-phaZ mutants were superior in surviving UV irradiation, hinting that PHA granule presence in bacterial cells is beneficial despite it being biologically inaccessible. Obtained data suggests that the ability to metabolize PHA although important for survival, probably is not the most crucial mechanism in the stress-resistance strategies arsenal of cold-loving bacteria. KEY POINTS: • PHA metabolism helps psychrophiles survive freezing • PHA-lacking psychrophile mutants cope better with oxidative and heat stresses • PHA granule presence enhances the UV resistance of psychrophiles.
- MeSH
- Bacteria metabolismus MeSH
- polyhydroxyalkanoáty * metabolismus MeSH
- uhlík metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
