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1.
Eur J Pharm Sci ; 203: 106925, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39374744

ABSTRACT

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70 % of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1 %, remaining stable for 8 h. Drug content decreased to ∼80 % after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70 % of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.


Subject(s)
Administration, Cutaneous , Dexamethasone , Hydrogen Sulfide , Skin , Hydrogen Sulfide/administration & dosage , Hydrogen Sulfide/chemistry , Dexamethasone/administration & dosage , Dexamethasone/chemistry , Animals , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Nanostructures/administration & dosage , Nanostructures/chemistry , Drug Delivery Systems/methods , Humans , Psoriasis/drug therapy , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry
2.
BMC Genomics ; 25(1): 884, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39304820

ABSTRACT

BACKGROUND: Kefir is a complex microbial community that plays a critical role in the fermentation and production of bioactive peptides, and has health-improving properties. The composition of kefir can vary by geographic localization and weather, and this paper focuses on a Brazilian sample and continues previous work that has successful anti-Alzheimer properties. In this study, we employed shotgun metagenomics and peptidomics approaches to characterize Brazilian kefir further. RESULTS: We successfully assembled the novel genome of Lactobacillus kefiranofaciens (LkefirU) and conducted a comprehensive pangenome analysis to compare it with other strains. Furthermore, we performed a peptidome analysis, revealing the presence of bioactive peptides encrypted by L. kefiranofaciens in the Brazilian kefir sample, and utilized in silico prospecting and molecular docking techniques to identify potential anti-Alzheimer peptides, targeting ß-amyloid (fibril and plaque), BACE, and acetylcholinesterase. Through this analysis, we identified two peptides that show promise as compounds with anti-Alzheimer properties. CONCLUSIONS: These findings not only provide insights into the genome of L. kefiranofaciens but also serve as a promising prototype for the development of novel anti-Alzheimer compounds derived from Brazilian kefir.


Subject(s)
Alzheimer Disease , Genome, Bacterial , Kefir , Lactobacillus , Microbiota , Peptides , Kefir/microbiology , Lactobacillus/genetics , Brazil , Peptides/chemistry , Peptides/pharmacology , Humans , Molecular Docking Simulation , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/genetics , Amyloid Precursor Protein Secretases/metabolism , Aspartic Acid Endopeptidases/genetics , Aspartic Acid Endopeptidases/metabolism , Metagenomics/methods
3.
Chemosphere ; 364: 143080, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39146989

ABSTRACT

Nanotechnology has brought significant advancements to agriculture through the development of engineered nanomaterials (ENPs). Silver nanoparticles (AgNPs) capped with polysaccharides have been applied in agricultural diagnostics, crop pest management, and seed priming. Hyaluronic acid (HA), a natural polysaccharide with bactericidal properties, has been considered a growth regulator for plant tissues and an inducer of systemic resistance against plant diseases. Additionally, HA has been employed as a stabilizing agent for AgNPs. This study investigated the synthesis and effects of hyaluronic acid-stabilized silver nanoparticles (HA-AgNPs) as a seed priming agent on lettuce (Lactuca sativa L.) seed germination. HA-AgNPs were characterized using several techniques, exhibiting spherical morphology and good colloidal stability. Germination assays conducted with 0.1, 0.04, and 0.02 g/L of HA-AgNPs showed a concentration-dependent reduction in seed germination. Conversely, lower concentrations of HA-AgNPs significantly increased germination rates, survival, tolerance indices, and seed water absorption compared to silver ions (Ag+). SEM/EDS indicated more significant potential for HA-AgNPs internalization compared to Ag+. Therefore, these findings are innovative and open new avenues for understanding the impact of Ag+ and HA-AgNPs on seed germination.


Subject(s)
Germination , Hyaluronic Acid , Lactuca , Metal Nanoparticles , Seeds , Silver , Lactuca/drug effects , Lactuca/growth & development , Silver/chemistry , Silver/toxicity , Silver/pharmacology , Germination/drug effects , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistry , Seeds/drug effects , Seeds/growth & development , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology
4.
Emerg Infect Dis ; 30(9): 1884-1894, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39174028

ABSTRACT

Malaria is increasingly diagnosed in urban centers across the Amazon Basin. In this study, we combined repeated prevalence surveys over a 4-year period of a household-based random sample of 2,774 persons with parasite genotyping to investigate the epidemiology of malaria in Mâncio Lima, the main urban transmission hotspot in Amazonian Brazil. We found that most malarial infections were asymptomatic and undetected by point-of-care microscopy. Our findings indicate that as malaria transmission decreases, the detection threshold of microscopy rises, resulting in more missed infections despite similar parasite densities estimated by molecular methods. We identified genetically highly diverse populations of Plasmodium vivax and P. falciparum in the region; occasional shared lineages between urban and rural residents suggest cross-boundary propagation. The prevalence of low-density and asymptomatic infections poses a significant challenge for routine surveillance and the effectiveness of malaria control and elimination strategies in urbanized areas with readily accessible laboratory facilities.


Subject(s)
Microscopy , Brazil/epidemiology , Humans , Prevalence , Microscopy/methods , Female , Male , Adult , Adolescent , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Child , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Malaria, Falciparum/prevention & control , Malaria/epidemiology , Malaria/transmission , Malaria/prevention & control , Malaria/parasitology , Plasmodium vivax/genetics , Urban Population , Child, Preschool , Plasmodium falciparum/genetics , Middle Aged , Young Adult , Infant , History, 21st Century
5.
Motor Control ; : 1-20, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39187237

ABSTRACT

Attentional focus strategies, especially external focus, are associated with improvements in mechanisms of postural control. This can be important in reducing sports injuries in practices such as running, which has seen an increase in adherence. However, the impacts of these strategies on postural control in runners are unclear. This study aimed to investigate the effects of internal and external focus strategies on postural control performance with different bases of support tasks in runners. A total of 19 young adults (18-38 years old) were divided into a running group (n = 9) and a control group (n = 10). Posturography tests were performed on stable and unstable surfaces, under control, and internal and external focus conditions. The distance, mean velocity, and total velocity of the center of pressure were analyzed (p ≤ .05). There was a reduction in oscillation under external focus compared to internal and control conditions, as well as under internal focus compared to the control condition. A Group × Surface × Focus interaction for the variables distance and mean velocity in the mediolateral direction was found only for the control group. However, no significant effects were found between groups for postural control performance. Attentional focus strategies were able to reduce postural sway, with external focus condition being the most effective. Practitioners can benefit from these strategies to increase postural control performance to help reduce the number of injuries and improve sports performance. It is speculated that the effects of attentional control strategies on postural control may differ depending on the specific adaptations of each sport.

6.
Microorganisms ; 12(6)2024 May 29.
Article in English | MEDLINE | ID: mdl-38930482

ABSTRACT

Due to its adsorption with aluminum and iron hydroxides, phosphorus viability is low in acidic soils; thus, the aim of this study was to isolate and identify bacteria from the rhizosphere of four legumes growing in acidic soils of the Cumbaza Sub-basin, San Martín, Peru, as well as to characterize their ability to solubilize aluminum phosphate and iron phosphate. The isolation process was conducted on TSA medium and the isolates were classified based on their origin and morphocolonial characteristics, with the bacillary shape being the most frequent, followed by cocci. To assess the solubilization of aluminum and iron phosphates, the liquid medium GELP was employed. Sixteen strains were selected, among which three stood out for their effectiveness in solubilizing AlPO4 (Sfcv-098-02, 22.65 mg L-1; Sfc-093-04, 26.50 mg L-1; and Sfcv-041-01-2, 55.98 mg L-1) and one for its ability to solubilize FePO4 (Sfcr-043-02, 32.61 mg L-1). These four strains were molecularly characterized, being identified as Enterobacter sp., Pseudomonas sp., and Staphylococcus sp. Additionally, a decrease in pH was observed in the reactions, with values ranging from 5.23 to 3.29, which enhanced the phosphate of solubilization. This suggests that the selected bacteria could be used to improve phosphorus availability in agricultural soils.

7.
BMC Neurol ; 24(1): 169, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783211

ABSTRACT

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.


Subject(s)
Myoclonic Epilepsies, Progressive , Seizures , Humans , Myoclonic Epilepsies, Progressive/complications , Myoclonic Epilepsies, Progressive/diagnosis , Seizures/diagnosis , Seizures/complications , Seizures/etiology , Seizures/drug therapy , Myoclonus/diagnosis , Myoclonus/etiology , Myoclonus/complications , Myoclonus/drug therapy , Male , Shaw Potassium Channels/genetics , Female , Electroencephalography/methods
8.
Nurs Inq ; 31(3): e12635, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38558441

ABSTRACT

Our goal was to explore self-care practices among men who have sex with men in the context of Mpox in Brazil. This study used qualitative research methods, including interviews and thematic analysis, to collect and analyze data from male participants across the Brazilian territory. The narratives unveil men's perspectives on self-care, risk reduction, and health beliefs during the Mpox pandemic. Our findings highlight a multifaceted approach to self-care among men, encompassing hygiene, physical contact management, mask usage, skin lesion vigilance, and adherence to official guidelines. Men's attitudes toward sexual behaviors emphasize the importance of reducing sexual partners, practicing safe sex, and combating misinformation through accurate information dissemination. The development of these behaviors and self-care practices can be facilitated by nurses guided by Dorothea Orem's Self-Care Theory, supported by patient-centered care, with strategies to address and confront the stigma associated with the disease and provide emotional support. Thus, the study underscores the pivotal role of self-care in mitigating infection risks, especially in the context of emerging infectious diseases. It acknowledges the impact of socio-cultural factors and healthcare policies on men's preventive measures. However, it also recognizes limitations, such as potential bias due to stigma concerns and a nonrepresentative sample. Ultimately, the research advocates for tailored education, promotion of gender equity, and healthcare empowerment to effectively manage health risks in such contexts.


Subject(s)
Communicable Diseases, Emerging , Qualitative Research , Self Care , Humans , Male , Brazil , Self Care/psychology , Adult , Communicable Diseases, Emerging/prevention & control , Homosexuality, Male/psychology , Middle Aged , Health Knowledge, Attitudes, Practice , Pandemics
9.
J Infect Dis ; 229(4): 947-958, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38324758

ABSTRACT

BACKGROUND: Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear. METHODS: We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention. RESULTS: We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission. CONCLUSIONS: P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Malaria , Humans , Malaria, Vivax/parasitology , Brazil/epidemiology , Prospective Studies , Malaria, Falciparum/parasitology , Prevalence , Plasmodium vivax , Plasmodium falciparum
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123773, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38142492

ABSTRACT

In this work, excitation-emission matrices (EEMs) were used in association with parallel factor analysis (PARAFAC) to assess biodiesel content in undiluted diesel-biodiesel blends (DBBs) without pre-sample preparation. EEMs were decomposed using the PARAFAC (EEMs-PARAFAC), and the loading values of the PARAFAC component as a function of biodiesel content in the blends were used to build an analytical model to quantify the biodiesel content in DBBs. The proposed model presenting a limit of detection (LOD) and a limit of quantification (LOQ) of 2.5% and 11% w/w, respectively, successfully predicted the biodiesel content in the validation samples. The robustness of the model was confirmed by a close analysis of the root mean square error of prediction, standard error of prediction, relative standard deviation of prediction, and Bias. Therefore, an accurate and robust analytical model based on EEMs-PARAFAC was developed to quantify the biodiesel content in undiluted DBBs without sample preparation.


Subject(s)
Biofuels , Biofuels/analysis , Spectrometry, Fluorescence/methods , Factor Analysis, Statistical
11.
Photodiagnosis Photodyn Ther ; 45: 103952, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38145771

ABSTRACT

The rise of antibiotic-resistant bacteria calls for innovative approaches to combat multidrug-resistant strains. Here, the potential of the standard histological stain, Giemsa, to act as a photosensitizer (PS) for antimicrobial photodynamic inactivation (aPDI) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains is reported. Bioassays were performed using various Giemsa concentrations (ranging from 0.0 to 20.0 µM) under 625 nm illumination at a light dose of 30 J cm-2. Remarkably, Giemsa completely inhibited the growth of MSSA and MRSA bacterial colonies for concentrations at 10 µM and higher but exhibited no inhibitory effect without light exposure. Partition coefficient analysis revealed Giemsa's affinity for membranes. Furthermore, we quantified the production of reactive oxygen species (ROS) and singlet oxygen (1O2) to elucidate the aPDI mechanisms underlying bacterial inactivation mediated by Giemsa. These findings highlight Giemsa stain's potential as a PS in aPDI for targeting multidrug-resistant bacteria.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Photochemotherapy , Staphylococcal Infections , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Azure Stains/pharmacology , Azure Stains/therapeutic use , Photochemotherapy/methods , Staphylococcus aureus , Anti-Infective Agents/therapeutic use , Staphylococcal Infections/drug therapy
12.
An Acad Bras Cienc ; 95(suppl 3): e20230710, 2023.
Article in English | MEDLINE | ID: mdl-38126383

ABSTRACT

We used Sentinel-2 imagery time series to generate a vegetation map for the Northern part of the Antarctica Peninsula and offshore islands, including the South Shetlands. The vegetation cover was identified in the NDVI maximum value composite image. The NDVI values were associated with the occurrence of algae (0.15 - 0.20), lichens (0.20 - 0.50), and mosses (0.50 - 0.80). The vegetation cover distribution map was validated using the literature information. Generating a vegetation map distribution on an annual basis was not possible due to high cloud cover in the Antarctic region, especially in coastal áreas, so optical images from 2016 to 2021 were necessary to map the vegetation distribution in the entire study área. The final map analyzed in association with the weather data shows the occurrence of a microenvironment over the western islands of the Antarctic Peninsula that provided vegetation growth conditions. The Sentinel-2 images with 10m spatial resolution allow the assembly of accurate vegetation distribution maps for the Antarctica Peninsula and Islands, the Google Earth Engine cloud computing being essential to process a large amount of the satellite images necessary for processing these maps.


Subject(s)
Bryophyta , Plants , Antarctic Regions
13.
Front Physiol ; 14: 1055706, 2023.
Article in English | MEDLINE | ID: mdl-37441000

ABSTRACT

Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch.

14.
Clin Anat ; 36(5): 787-794, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36942964

ABSTRACT

Longitudinal dissociation of the aggregated specialized cardiomyocytes within the non-branching portion of atrioventricular conduction axis has proved a controversial topic for both morphologists and electrophysiologists. We have now used morphological methods, including three-dimensional assessment, to revisit, in human, canine, and bovine hearts, the presence or absence of interconnections between the aggregated cardiomyocytes making up the non-branching bundle. We analyzed three datasets from human and canine hearts, and two from bovine hearts, using longitudinal and orthogonal serial histological sections. In addition, we assessed three hearts using translucent India ink injected specimens, permitting assessment of the three-dimensional arrangement of the cardiomyocytes. Using the longitudinal sections, we found numerous oblique interconnections between the groups of specialized cardiomyocytes. When assessing orthogonal sections, we noted marked variation in the grouping of the cardiomyocytes. We interpreted this finding as evidence of bifurcation and convergence of the groups seen in the longitudinal sections. The three-dimensional assessment of the bovine material confirmed the presence of the numerous interconnections. The presence of multiple connections between the cardiomyocytes in the non-branching bundle rules out the potential for longitudinal dissociation.


Subject(s)
Atrioventricular Node , Heart Conduction System , Animals , Dogs , Cattle , Humans , Heart Conduction System/anatomy & histology , Atrioventricular Node/pathology , Bundle of His/pathology
15.
J Chem Inf Model ; 63(7): 1999-2013, 2023 04 10.
Article in English | MEDLINE | ID: mdl-36952668

ABSTRACT

We present TopIso3D Viewer, a software with a user-friendly graphical interface, that generates three-dimensional maps to analyze descriptors based on the Quantum Theory of Atoms in Molecules (QTAIM), applied in periodic and nonperiodic systems. The software also automates the launching of topological analysis calculations through the Topond package and generates a report that facilitates the identification of the values of the calculated descriptors, in the Bond Critical Points (BCP) and Critical Points of the Laplacian of the electron density (LCP), facilitating the classification of chemical interactions. The map projects created can be stored in the form of HTML files, for later consultation through any type of browser. For validation of the software, several systems with 0-3D dimensions were studied. In addition, the topology of urea molecular crystal and its isolated molecule were revisited.


Subject(s)
Quantum Theory , Software , Models, Molecular
16.
ACS Nano ; 17(8): 7417-7430, 2023 04 25.
Article in English | MEDLINE | ID: mdl-36877273

ABSTRACT

In the present study we evaluate the effect of superparamagnetic iron oxide nanoparticles (SPIONs) carrying usnic acid (UA) as chemical cargo on the soil microbial community in a dystrophic red latosol (oxysol). Herein, 500 ppm UA or SPIONs-framework carrying UA were diluted in sterile ultrapure deionized water and applied by hand sprayer on the top of the soil. The experiment was conducted in a growth chamber at 25 °C, with a relative humidity of 80% and a 16 h/8 h light-dark cycle (600 lx light intensity) for 30 days. Sterile ultrapure deionized water was used as the negative control; uncapped and oleic acid (OA) capped SPIONs were also tested to assess their potential effects. Magnetic nanostructures were synthesized by a coprecipitation method and characterized by scanning and transmission electron microscopy (SEM and TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), zeta potential, hydrodynamic diameter, magnetic measurements, and release kinetics of chemical cargo. Uncapped and OA-capped SPIONs did not significantly affect soil microbial community. Our results showed an impairment in the soil microbial community exposed to free UA, leading to a general decrease in negative effects on soil-based parameters when bioactive was loaded into the nanoscale magnetic carrier. Besides, compared to control, the free UA caused a significant decrease in microbial biomass C (39%), on the activity of acid protease (59%), and acid phosphatase (23%) enzymes, respectively. Free UA also reduced eukaryotic 18S rRNA gene abundance, suggesting a major impact on fungi. Our findings indicate that SPIONs as bioherbicide nanocarriers can reduce the negative impacts on soil. Therefore, nanoenabled biocides may improve agricultural productivity, which is important for food security due to the need of increasing food production.


Subject(s)
Magnetite Nanoparticles , Magnetite Nanoparticles/chemistry , Soil , Magnetic Iron Oxide Nanoparticles , Water
17.
Nat Commun ; 14(1): 199, 2023 01 13.
Article in English | MEDLINE | ID: mdl-36639383

ABSTRACT

Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-905 shows good oral absorption, its metabolites are stable, achieving long-lasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.


Subject(s)
Antiviral Agents , COVID-19 , Animals , Humans , Mice , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , SARS-CoV-2 , Kinetin/pharmacology , Inflammation/drug therapy , Nucleotides , Virus Replication
18.
Sensors (Basel) ; 24(1)2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38202991

ABSTRACT

A miniaturized and low-cost electrochemical 3D-printed system for rapid and accurate quantification of ethanol content in ethanol fuel using electrochemical impedance spectroscopy (EIS) was developed. The monolithic design of the system incorporates insulating thermoplastic electrode separators, with only the cover being mobile, allowing for easy assembly and handling. The portable device, measuring approximately 26 × 24 mm, has a maximum capacity of 1 mL, making it suitable for lab-on-a-chip and portable analysis. By utilizing the dielectric constant of ethanol and ethanol fuel mixtures with water, the miniaturized EIS cell quantifies ethanol content effectively. To validate its performance, we compared measurements from four gas stations with a digital densimeter, and the values obtained from the proposed system matched perfectly. Our miniaturized and low-cost electrochemical 3D-printed device can be printed and assembled in two hours, offering a cost-effective solution for fast and precise ethanol quantification. Its versatility, affordability, and compatibility with lab-on-a-chip platforms make it easily applicable, including for fuel quality control and on-site analysis in remote locations.

19.
J Chem Phys ; 157(21): 214303, 2022 Dec 07.
Article in English | MEDLINE | ID: mdl-36511526

ABSTRACT

In this work, the pressure- and temperature-dependent reaction rate constants for the hydrogen abstraction and addition of hydroxyl radicals to the unsaturated cyclopentene were studied. Geometries and vibrational frequencies of reactants, products, and transition states were calculated using density functional theory, with single-point energy corrections determined at the domain-based local pair natural orbital-coupled-cluster single double triple/cc-pVTZ-F12 level. The high-pressure limit rate constants were calculated using the canonical variational transition state theory with the small-curvature tunneling approximation. The vibrational partition functions were corrected by the effects of torsional and ring-puckering anharmonicities of the transition states and cyclopentene, respectively. Variational effects are shown to be relevant for all the hydrogen abstraction reactions. The increasing of the rate constants by tunneling is significant at temperatures below 500 K. The pressure dependence on the rate constants of the addition of OH• to cyclopentene was calculated using the system-specific quantum Rice-Ramsperger-Kassel model. The high-pressure limit rate constants decrease with increasing temperature in the range 250-1000 K. The falloff behavior was studied at several temperatures with pressures varying between 10-3 and 103 bar. At temperatures below 500 K, the effect of the pressure on the addition rate constant is very modest. However, at temperatures around and above 1000 K, taking pressure into account is mandatory for an accurate rate constant calculation. Branching ratio analyses reveal that the addition reaction dominates at temperatures below 500 K, decreasing rapidly at higher temperatures. Arrhenius parameters are provided for all reactions and pressure dependent Arrhenius parameters are given for the addition of OH• to cyclopentene.

20.
Polymers (Basel) ; 14(22)2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36433149

ABSTRACT

The use of biocompatible and low-cost polymeric matrices to produce non-phytotoxic nanoparticles for delivery systems is a promising alternative for good practices in agriculture management and biotechnological applications. In this context, there is still a lack of studies devoted to producing low-cost polymeric nanoparticles that exhibit non-phytotoxic properties. Among the different polymeric matrices that can be used to produce low-cost nanoparticles, we can highlight the potential application of cellulose acetate, a natural biopolymer with biocompatible and biodegradable properties, which has already been used as fibers, membranes, and films in different agricultural and biotechnological applications. Here, we provided a simple and low-cost route to produce cellulose acetate nanoparticles (CA-NPs), by modified emulsification solvent evaporation technique, with a main diameter of around 200 nm and a spherical and smooth morphology for potential use as agrochemical nanocarriers. The non-phytotoxic properties of the produced cellulose acetate nanoparticles were proved by performing a plant toxic test by Allium cepa assay. The cytotoxicity and genotoxicity tests allowed us to evaluate the mitotic process, chromosomal abnormalities, inhibition/delay in root growth, and micronucleus induction. In summary, the results demonstrated that CA-NPs did not induce phytotoxic, cytotoxic, or genotoxic effects, and they did not promote changes in the root elongation, germination or in the mitotic, chromosomal aberration, and micronucleus indices. Consequently, the present findings indicated that CA-NPs can be potentially used as environmentally friendly nanoparticles.

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