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1.
Biotechnol J ; 19(7): e2400170, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39014932

RESUMO

Therapeutic oligonucleotides (ONs) have great potential to treat many diseases due to their ability to regulate gene expression. However, the inefficiency of standard purification techniques to separate the target sequence from molecularly similar variants is hindering development of large scale ON manufacturing at a reasonable cost. Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) is a valuable process able to bypass the purity-yield tradeoff typical of single-column operations, and hence to make the ON production more sustainable from both an economic and environmental point of view. However, operating close to the optimum of MCSGP can be challenging, resulting in unstable process performance and in a drift in product quality, especially when running a continuous process for extended periods where process parameters such as temperature are prone to variation. In this work, we demonstrate how greater process robustness is introduced in the design and execution of MCSGP for the purification of a 20mer single-stranded DNA sequence through the implementation of UV-based dynamic control. With this novel approach, the cyclic steady state was reached already in the third cycle and disturbances coming from fluctuations in the feed quality, loading amount and temperature were effectively compensated allowing a stable operation close to the optimum. In response to the perturbations, the controlled process kept the standard deviation on product recovery below 3.4%, while for the non-controlled process it increased up to 27.5%.


Assuntos
Oligonucleotídeos , Solventes , Oligonucleotídeos/química , Oligonucleotídeos/isolamento & purificação , Solventes/química , Distribuição Contracorrente/métodos , Raios Ultravioleta , Temperatura , DNA de Cadeia Simples/química , DNA de Cadeia Simples/isolamento & purificação
2.
J Mol Model ; 30(8): 255, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970658

RESUMO

CONTEXT: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients. METHODS: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program.


Assuntos
Antioxidantes , Desenho Assistido por Computador , Desenho de Fármacos , Resveratrol , Protetores Solares , Raios Ultravioleta , Protetores Solares/química , Antioxidantes/química , Antioxidantes/farmacologia , Resveratrol/química , Propiofenonas/química , Teoria da Densidade Funcional , Estilbenos/química , Estilbenos/farmacologia , Modelos Moleculares , Teoria Quântica , Estrutura Molecular
3.
Cells ; 13(13)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38995009

RESUMO

We developed an automated microregistration method that enables repeated in vivo skin microscopy imaging of the same tissue microlocation and specific cells over a long period of days and weeks with unprecedented precision. Applying this method in conjunction with an in vivo multimodality multiphoton microscope, the behavior of human skin cells such as cell proliferation, melanin upward migration, blood flow dynamics, and epidermal thickness adaptation can be recorded over time, facilitating quantitative cellular dynamics analysis. We demonstrated the usefulness of this method in a skin biology study by successfully monitoring skin cellular responses for a period of two weeks following an acute exposure to ultraviolet light.


Assuntos
Pele , Humanos , Pele/citologia , Pele/diagnóstico por imagem , Raios Ultravioleta , Rastreamento de Células/métodos , Proliferação de Células , Movimento Celular , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Microscopia/métodos
4.
J Photochem Photobiol B ; 257: 112975, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38970967

RESUMO

The physiological parameters such as growth, Chl a content, and photosynthetic performance of the experimental cyanobacterium Anabaenopsis circularis HKAR-22 were estimated to evaluate the cumulative effects of photosynthetically active radiation (PAR) and ultraviolet (UV) radiation. Maximum induction of UV-screening molecules, MAAs, was observed under the treatment condition of PAR + UV-A + UV-B (PAB) radiations. UV/VIS absorption spectroscopy and HPLC-PDA detection primarily confirmed the presence of MAA-shinorine (SN) having absorption maxima (λmax) at 332.3 nm and retention time (RT) of 1.47 min. For further validation of the presence of SN, HRMS, FTIR and NMR were utilized. UV-stress elevated the in vivo ROS scavenging and in vitro enzymatic antioxidant capabilities. SN exhibited substantial and concentration-dependent antioxidant capabilities which was determined utilizing 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate (ABTS), ferric reducing power (FRAP) and superoxide radical scavenging assay (SRSA). The density functional theory (DFT) method using B3LYP energy model and 6-311G++(d,p) basis set was implied to perform the quantum chemical calculation to systematically investigate the antioxidant nature of SN. The principal pathways involved in the antioxidant reactions along with the basic molecular descriptors affecting the antioxidant potentials of a compound were also studied. The results favor the potential of SN as an active ingredient to be used in cosmeceutical formulations.


Assuntos
Antioxidantes , Cianobactérias , Teoria da Densidade Funcional , Raios Ultravioleta , Antioxidantes/química , Cianobactérias/química , Cianobactérias/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Cicloexanonas/química , Fotossíntese , Espécies Reativas de Oxigênio/metabolismo , Clorofila A/química , Clorofila A/metabolismo , Compostos de Bifenilo/química , Picratos/antagonistas & inibidores , Picratos/química , Sequestradores de Radicais Livres/química , Cicloexilaminas , Glicina/análogos & derivados , Ácidos Sulfônicos , Benzotiazóis
5.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000160

RESUMO

222 nm far-ultraviolet (F-UV) light has a bactericidal effect similar to deep-ultraviolet (D-UV) light of about a 260 nm wavelength. The cytotoxic effect of 222 nm F-UV has not been fully investigated. DLD-1 cells were cultured in a monolayer and irradiated with 222 nm F-UV or 254 nm D-UV. The cytotoxicity of the two different wavelengths of UV light was compared. Changes in cell morphology after F-UV irradiation were observed by time-lapse imaging. Differences in the staining images of DNA-binding agents Syto9 and propidium iodide (PI) and the amount of cyclobutane pyrimidine dimer (CPD) were examined after UV irradiation. F-UV was cytotoxic to the monolayer culture of DLD-1 cells in a radiant energy-dependent manner. When radiant energy was set to 30 mJ/cm2, F-UV and D-UV showed comparable cytotoxicity. DLD-1 cells began to expand immediately after 222 nm F-UV light irradiation, and many cells incorporated PI; in contrast, PI uptake was at a low level after D-UV irradiation. The amount of CPD, an indicator of DNA damage, was higher in cells irradiated with D-UV than in cells irradiated with F-UV. This study proved that D-UV induced apoptosis from DNA damage, whereas F-UV affected membrane integrity in monolayer cells.


Assuntos
Apoptose , Membrana Celular , Neoplasias do Colo , Dano ao DNA , Raios Ultravioleta , Humanos , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/efeitos da radiação , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Apoptose/efeitos da radiação , Dímeros de Pirimidina/metabolismo
7.
J Drugs Dermatol ; 23(7): 575-577, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954618

RESUMO

BACKGROUND: To understand the prevalence and types of publications addressing darker skin types within the existing evidence base for sunscreen use.  Evidence Review: PubMed was searched from 1988, the time point at which the first skin of color (SOC) article was identified, through December 2022 using PubMed's Medical Subject Headings terms and keyword searches in title and abstract, with and without terms for SOC and ethnicity. Identified articles were reviewed for relevance, de-duplicated, and categorized; results are summarized. FINDINGS: Of the 5927 articles on sunscreen overall, only 314 (5.3%) articles addressed SOC, with the majority published since 2007 and representing only 4% to 7% of total publications annually except in 2022 when the proportion of SOC articles was 23.5%. Of the articles on SOC, many reported sunscreen knowledge and patient behaviors (29%), but very few reported clinical trials (5%). The 3 conditions most often discussed were melasma, post-inflammatory hyperpigmentation, and dyschromia. South Asian ethnicities (India, Pakistan, Bangladesh) had the highest representation within the literature, followed by Hispanics. CONCLUSIONS AND RELEVANCE: Although it was assumed there would be fewer papers discussing the use of sunscreen in darker skin types, the scale of the disparity revealed by this study is stark. The increase in a number of articles in 2022 suggests an increasing focus on SOC, but further discussion of the issues presented here will help the SOC community address gaps in the evidence base and better inform discussions on sunscreen and photoprotection between clinicians and patients.J Drugs Dermatol. 2024;23(7):575-577.  doi:10.36849/JDD.8250.


Assuntos
Pigmentação da Pele , Protetores Solares , Humanos , Protetores Solares/administração & dosagem , Pigmentação da Pele/efeitos dos fármacos , Conhecimentos, Atitudes e Prática em Saúde , Raios Ultravioleta/efeitos adversos
8.
Environ Sci Technol ; 58(28): 12621-12632, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38954776

RESUMO

The majority of microplastics (MPs) found in the environment originate from plastic fragmentation occurring in the environment and are influenced by environmental factors such as UV irradiation and biotic interactions. However, the effects of river drying on plastic fragmentation remain unknown, despite the global prevalence of watercourses experiencing flow intermittence. This study investigates, through laboratory experiments, the coupled effects of drying duration and UV irradiation on PVC film fragmentation induced by artificial mechanical abrasion. This study shows that PVC film fragmentation increases with drying duration through an increase in the abundance and size of formed MPs as well as mass loss from the initial plastic item, with significant differences for drying durations >50% of the experiment duration. The average abundance of formed MPs in treatments exposed to severe drying duration was almost two times higher than in treatments nonexposed to drying. Based on these results, we developed as a proof of concept an Intermittence-Based Plastic Fragmentation Index that may provide insights into plastic fragmentation occurring in river catchments experiencing large hydrological variability. The present study suggests that flow intermittence occurring in rivers and streams can lead to increasing plastic fragmentation, unraveling new insights into plastic pollution in freshwater systems.


Assuntos
Microplásticos , Cloreto de Polivinila , Rios , Rios/química , Cloreto de Polivinila/química , Poluentes Químicos da Água , Raios Ultravioleta , Monitoramento Ambiental , Dessecação
9.
Anal Chem ; 96(28): 11525-11532, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38966896

RESUMO

The urgent need for field detection of uranium in seawater is 2-fold: to provide prompt guidance for uranium extraction and to prevent human exposure to nuclear radiation. However, current methods for this purpose are largely hindered by bulky instrumentation, high costs of developed materials, and severe matrix interferences, which limit their further application in the field. Herein, we demonstrated a portable and label-free strategy for the field detection of uranyl in seawater based on the efficient photocleavage of DNA. Further experiments confirmed the generation of ultraviolet (UV) light-induced reactive oxygen species (ROS), such as O2•- and •OH, which fragmented oligomeric DNA in the presence of uranyl and UV light. Detailed studies showed that DNA significantly enhances uranyl absorption in the UV-visible region, leading to the generation of more ROS. A fluorescence system for the selective detection of uranyl in seawater was established by immobilizing two complementary oligonucleotides with the fluorescent dye SYBR Green I. The strategy of UV-induced photocleavage offers high selectivity, excellent interference immunity, and high sensitivity for uranyl, with a detection limit of 6.8 nM. Additionally, the fluorescence can be visually detected using a 3D-printed miniaturized device integrated with a smartphone. This method has been successfully applied to the on-site detection of uranyl in seawater in 18 Chinese coastal cities and along the coast of Hainan Island within 3 min for a single sample. The sample testing and field analysis results indicate that this strategy has promising potential for real-time monitoring of trace uranyl in China's coastal waters. It is expected to be utilized for the rapid assessment of nuclear contamination and nuclear engineering construction.


Assuntos
DNA , Água do Mar , Raios Ultravioleta , Urânio , Água do Mar/análise , Água do Mar/química , DNA/análise , China , Urânio/análise , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/análise , Limite de Detecção , Processos Fotoquímicos , Diaminas , Benzotiazóis/química , Compostos Orgânicos/análise , Compostos Orgânicos/química , Quinolinas
10.
J Agric Food Chem ; 72(28): 15498-15511, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38950542

RESUMO

UV can serve as an effective light spectrum for regulating plant secondary metabolites, while relevant studies on UV-A are much less extensive than those on UV-B. A comprehensive understanding of the selective effects of UV-A on different secondary metabolites and the specific features of primary metabolism that drive these effects is still lacking. To address this knowledge gap, we conducted a study to analyze the dynamic changes in the metabolome and transcriptome of lettuce leaves irradiated with red plus UV-A light (monochromatic red light as control). Generally, UV-A promoted the synthesis of most phenylpropanoids and terpenoids originating from the shikimate and methylerythritol phosphate (MEP) pathway in plastids but sacrificed the synthesis of terpenoids derived from the mevalonate (MVA) pathway, particularly sesquiterpenes. Increased precursors supply for the shikimate and MEP pathway under UV-A was directly supported by the activation of the Calvin-Benson cycle and phosphoenolpyruvate transport. Whereas, along with phosphoenolpyruvate transport, the TCA cycle was restrained, causing deprivation of the MVA pathway precursor. In addition, UV-A also activated the plastidic oxidative branch of the pentose phosphate pathway, photorespiration, and malate shuttle, to ensure a sufficient supply of nitrogen, circulation homeostasis of the Calvin-Benson cycle, and energy balance, thus indirectly supporting UV-A-induced specific secondary metabolic output. This study provides a comprehensive framework for understanding the flexible primary-secondary metabolism interactions that are able to produce specific metabolites favorable for adaptation to environmental stimuli.


Assuntos
Lactuca , Folhas de Planta , Metabolismo Secundário , Raios Ultravioleta , Lactuca/metabolismo , Lactuca/efeitos da radiação , Lactuca/química , Lactuca/genética , Lactuca/crescimento & desenvolvimento , Metabolismo Secundário/efeitos da radiação , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Folhas de Planta/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Metaboloma/efeitos da radiação , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Multiômica
11.
Sci Rep ; 14(1): 15963, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987323

RESUMO

The recent COVID-19 pandemic has raised interest in efficient air disinfection solutions. The application of germicidal ultraviolet (GUV) irradiation is an excellent contender to prevent airborne transmission of COVID-19, as well as other existing and future infectious airborne diseases. While GUV has already been proven effective in inactivating SARS-CoV-2, quantitative data on UV susceptibility and dose requirements, needed to predict and optimize the performance of GUV solutions, is still limited. In this study, the UV susceptibility of aerosolized SARS-CoV-2 to 254 nm ultraviolet (UV) irradiation is investigated. This is done by employing 3D computational fluid dynamics based simulations of SARS-CoV-2 inactivation in a test chamber equipped with an upper-room UV-C luminaire and comparing the results to previously published measurements performed in the same test chamber. The UV susceptibility found in this study is (0.6 ± 0.2) m2/J, which is equivalent to a D90 dose between 3 and 6 J/m2. These values are in the same range as previous estimations based on other corona viruses and inactivation data reported in literature.


Assuntos
COVID-19 , Desinfecção , SARS-CoV-2 , Raios Ultravioleta , SARS-CoV-2/efeitos da radiação , Desinfecção/métodos , COVID-19/prevenção & controle , COVID-19/virologia , COVID-19/transmissão , Humanos , Aerossóis , Hidrodinâmica , Simulação por Computador , Inativação de Vírus/efeitos da radiação
12.
PLoS One ; 19(7): e0299421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954713

RESUMO

Mold infestations in buildings pose significant challenges to human health, affecting both private residences and hospitals. While molds commonly trigger asthma and allergies in the immunocompetent, they can cause life-threatening diseases in the immunocompromised. Currently, there is an unmet need for new strategies to reduce or prevent mold infestations. Far-UVC technology can inactivate microorganisms while remaining safe for humans. This study investigates the inhibitory efficacy of far-UVC light at 222 nm on the growth of common mold-producing fungi, specifically Penicillium candidum, when delivered in low-dose on-off duty cycles, a configuration consistent with its use in real-world settings. The inhibitory effect of the low-dose duty cycles was assessed on growth induced by i) an adjacent spore-producing P. candidum donor and ii) P. candidum spores seeded directly onto agar plates. In both setups, the far-UVC light significantly inhibited both vertical and horizontal growth of P. candidum, even when the UV doses were below the Threshold Value Limit of 23 mJ/cm2. These results suggest that far-UVC light holds the potential to improve indoor air quality by reducing or preventing mold growth, also when people are present.


Assuntos
Penicillium , Raios Ultravioleta , Penicillium/crescimento & desenvolvimento , Penicillium/efeitos da radiação , Esporos Fúngicos/efeitos da radiação , Esporos Fúngicos/crescimento & desenvolvimento , Fungos/efeitos da radiação , Fungos/crescimento & desenvolvimento , Humanos , Poluição do Ar em Ambientes Fechados/prevenção & controle , Poluição do Ar em Ambientes Fechados/análise , Níveis Máximos Permitidos
13.
Invest Ophthalmol Vis Sci ; 65(8): 8, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958968

RESUMO

Purpose: The purpose of this study was to evaluate the biomechanical and hydration differences in scleral tissue after two modalities of collagen cross-linking. Methods: Scleral tissue from 40 adult white rabbit eyes was crosslinked by application of 0.1% Rose Bengal solution followed by 80 J/cm2 green light irradiation (RGX) or by application of 0.1% riboflavin solution followed by 5.4 J/cm2 ultraviolet A irradiation (UVX). Posterior scleral strips were excised from treated and untreated sclera for tensile and hydration-tensile tests. For tensile tests, the strips were subjected to uniaxial extension after excision. For hydration-tensile tests, the strips were dehydrated, rehydrated, and then tested. Young's modulus at 8% strain and swelling rate were estimated. ANOVAs were used to test treated-induced differences in scleral biomechanical and hydration properties. Results: Photo-crosslinked sclera tissue was stiffer (Young's modulus at 8% strain: 10.7 ± 4.5 MPa, on average across treatments) than untreated scleral tissue (7.1 ± 4.0 MPa). Scleral stiffness increased 132% after RGX and 90% after UVX compared to untreated sclera. Scleral swelling rate was reduced by 11% after RGX and by 13% after UVX. The stiffness of the treated sclera was also associated with the tissue hydration level. The lower the swelling, the higher the Young's modulus of RGX (-3.8% swelling/MPa) and UVX (-3.5% swelling/MPa) treated sclera. Conclusions: Cross-linking with RGX and UVX impacted the stiffness and hydration of rabbit posterior sclera. The Rose Bengal with green light irradiation may be an alternative method to determine the efficacy and suitability of inducing scleral tissue stiffening in the treatment of myopia.


Assuntos
Reagentes de Ligações Cruzadas , Fármacos Fotossensibilizantes , Riboflavina , Rosa Bengala , Esclera , Raios Ultravioleta , Animais , Coelhos , Reagentes de Ligações Cruzadas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Rosa Bengala/farmacologia , Resistência à Tração , Fenômenos Biomecânicos , Módulo de Elasticidade , Colágeno/metabolismo , Elasticidade
14.
Nat Commun ; 15(1): 5508, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951161

RESUMO

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.


Assuntos
Reagentes de Ligações Cruzadas , Grafite , Oxigênio , Pontos Quânticos , Riboflavina , Pontos Quânticos/química , Animais , Grafite/química , Oxigênio/metabolismo , Riboflavina/farmacologia , Coelhos , Masculino , Reagentes de Ligações Cruzadas/química , Compostos de Nitrogênio/química , Espécies Reativas de Oxigênio/metabolismo , Ceratocone/tratamento farmacológico , Ceratocone/metabolismo , Raios Ultravioleta , Córnea/efeitos dos fármacos , Córnea/metabolismo , Córnea/patologia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Substância Própria/metabolismo , Substância Própria/efeitos dos fármacos
15.
Sci Rep ; 14(1): 15395, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965255

RESUMO

The APOBEC/AID family is known for its mutator activity, and recent evidence also supports the potential impact of ADARs. Furthermore, the mutator impacts of APOBEC/ADAR mutations have not yet been investigated. Assessment of pancancer TCGA exomes identified enriched somatic variants among exomes with nonsynonymous APOBEC1, APOBEC3B, APOBEC3C, ADAR, and ADARB1 mutations, compared to exomes with synonymous ones. Principal component (PC) analysis reduced the number of potential players to eight in cancer exomes/genomes, and to five in cancer types. Multivariate regression analysis was used to assess the impact of the PCs on each COSMIC mutational signature among pancancer exomes/genomes and particular cancers, identifying several novel links, including SBS17b, SBS18, and ID7 mainly determined by APOBEC1 mRNA levels; SBS40, ID1, and ID2 by age; SBS3 and SBS16 by APOBEC3A/APOBEC3B mRNA levels; ID5 and DBS9 by DNA repair/replication (DRR) defects; and SBS7a-d, SBS38, ID4, ID8, ID13, and DBS1 by ultraviolet (UV) radiation/ADARB1 mRNA levels. APOBEC/ADAR mutations appeared to potentiate the impact of DRR defects on several mutational signatures, and some factors seemed to inversely affect certain signatures. These findings potentially implicate certain APOBEC/ADAR mutations/mRNA levels in distinct mutational signatures, particularly APOBEC1 mRNA levels in aging-related signatures and ADARB1 mRNA levels in UV radiation-related signatures.


Assuntos
Adenosina Desaminase , Envelhecimento , Mutação , RNA Mensageiro , Proteínas de Ligação a RNA , Raios Ultravioleta , Humanos , Raios Ultravioleta/efeitos adversos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Envelhecimento/genética , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Desaminase APOBEC-1/genética , Desaminase APOBEC-1/metabolismo , Desaminases APOBEC/genética , Desaminases APOBEC/metabolismo , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Neoplasias/genética , Exoma
16.
Se Pu ; 42(7): 681-692, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-38966976

RESUMO

Dynamic changes in the structures and interactions of proteins are closely correlated with their biological functions. However, the precise detection and analysis of these molecules are challenging. Native mass spectrometry (nMS) introduces proteins or protein complexes into the gas phase by electrospray ionization, and then performs MS analysis under near-physiological conditions that preserve the folded state of proteins and their complexes in solution. nMS can provide information on stoichiometry, assembly, and dissociation constants by directly determining the relative molecular masses of protein complexes through high-resolution MS. It can also integrate various MS dissociation technologies, such as collision-induced dissociation (CID), surface-induced dissociation (SID), and ultraviolet photodissociation (UVPD), to analyze the conformational changes, binding interfaces, and active sites of protein complexes, thereby revealing the relationship between their interactions and biological functions. UVPD, especially 193 nm excimer laser UVPD, is a rapidly evolving MS dissociation method that can directly dissociate the covalent bonds of protein backbones with a single pulse. It can generate different types of fragment ions, while preserving noncovalent interactions such as hydrogen bonds within these ions, thereby enabling the MS analysis of protein structures with single-amino-acid-site resolution. This review outlines the applications and recent progress of nMS and UVPD in protein dynamic structure and interaction analyses. It covers the nMS techniques used to analyze protein-small-molecule ligand interactions, the structures of membrane proteins and their complexes, and protein-protein interactions. The discussion on UVPD includes the analysis of gas-phase protein structures and interactions, as well as alterations in protein dynamic structures, and interactions resulting from mutations and ligand binding. Finally, this review describes the future development prospects for protein analysis by nMS and new-generation advanced extreme UV light sources with higher brightness and shorter pulses.


Assuntos
Espectrometria de Massas , Proteínas , Raios Ultravioleta , Proteínas/química , Espectrometria de Massas/métodos , Conformação Proteica
17.
Sci Rep ; 14(1): 16614, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025900

RESUMO

Dynamic deformation events induced by osmosis or photochemical stiffening substantially influence geometrical and mechanical assessments in post-mortem corneas, therefore need to be carefully monitored in experimental settings. In this study, we employed optical coherence elastography (OCE) to quantify dynamic deformation processes at high resolution in freshly enucleated porcine corneas. Osmotic effects were studied by immerging n = 9 eyes in preservation media of three different tonicities. Dynamic processes underlying corneal cross-linking (CXL) were studied by subjecting n = 6 eyes to standard Dresden treatment, while three control groups were used. The entire procedures were performed under an OCE setup during up to 80 min, acquiring a volumetric scan every 20 s. Changes in OCE-derived axial deformations were incrementally calculated between consecutive scans. Preservation conditions had a strong influence on the observed strain patterns, which were consistent with the tonicity of the medium (swelling in hypotonic, deswelling in hypertonic environment). In the CXL group, we observed deswelling of the anterior stroma 10 min after starting the UV irradiation, which was not observed in any control group (p = 0.007). The presented results proved OCE to be a valuable technique to quantify subtle dynamic biomechanical alterations in the cornea resulting from CXL and preservation solutions.


Assuntos
Córnea , Reagentes de Ligações Cruzadas , Técnicas de Imagem por Elasticidade , Tomografia de Coerência Óptica , Animais , Técnicas de Imagem por Elasticidade/métodos , Suínos , Córnea/efeitos dos fármacos , Córnea/diagnóstico por imagem , Córnea/metabolismo , Reagentes de Ligações Cruzadas/farmacologia , Tomografia de Coerência Óptica/métodos , Osmose , Raios Ultravioleta , Difusão , Crosslinking Corneano
18.
Vet Med Sci ; 10(4): e1497, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952252

RESUMO

BACKGROUND: Annually, a massive amount of broiler litter (BL) is produced in the world, which causes soil and surface water pollution due to its high nitrogen content and microbial count. While ruminants can use this non-protein nitrogen (NPN) source for microbial protein synthesis. This issue becomes more critical when protein sources are unavailable or very expensive. One of the sources of NPN is BL which is produced at a considerable amount in the world yearly. OBJECTIVES: This aim of this research was to conduct a survey of non-thermal technologies such as electrocoagulation (EC), ultraviolet (UV) radiation, and ultrasound (US) waves on the microbial safety and nutritional value of BL samples as a protein source in ruminant diets. MATERIALS AND METHODS: The methodology of this study was based on the use of an EC device with 24 V for 60 min, UV-C light radiation (249 nm) for 1 and 10 min, and US waves with a frequency of 28 kHz for 5, 10 and 15 min to process BL samples compared with shade-dried samples. Chemical composition and nutritional values of processed samples were determined by gas production technique and measurement of fermentation parameters in vitro. RESULTS: Based on the results, microbial safety increased in the samples processed with the US (15 min). The EC method had the best performance in reducing the number of fungi and mould. However, none of the methods could remove total bacteria and fungi. Digestibility of BL was similar in shade-dried, EC, and US (10 min) treatments. In general, the use of EC and US15 without having adverse effects on gas production caused a decrease in the concentration of ammonia nitrogen. In contrast, it caused a decrease in neutral detergent fibre (NDF) in the investigated substrate. CONCLUSIONS: In general, it can be concluded that the use of US5 and EC methods without having a negative effect on the parameters of gas production and fermentation in vitro, while reducing NDF, causes a significant reduction in the microbial load, pathogens, yeast, and mould. Therefore, it is suggested to use these two methods to improve feed digestibility for other protein and feed sources.


Assuntos
Galinhas , Fermentação , Valor Nutritivo , Raios Ultravioleta , Animais , Ondas Ultrassônicas , Esterco/análise , Esterco/microbiologia
19.
J Drugs Dermatol ; 23(7): 504-509, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954621

RESUMO

Photoaging is a complex, ongoing process that clinically manifests as cutaneous rhytides, atrophy, laxity, dyspigmentation, telangiectasias, roughness, and mottled appearance of the skin. There is an abundance of research establishing the mechanism of ultraviolet (UV) - induced photodamage as it is a significant source of photoaging and skin cancers. While UV damage is known to induce photoaging, it is important to understand how other forms of light radiation also contribute to this process. UV only constitutes 5 to 10% of solar radiation that reaches the earth's surface. The remaining nearly 90% is evenly split between infrared and visible light radiation. Early research shows that varied skin types may elicit different photobiologic responses to light. This article presents the mechanisms and biomarkers of photodamage induced by light from across the spectrum, including UV, visible light, and infrared to better prevent and reverse the damage of photoaging in all skin types.J Drugs Dermatol. 2024;23(7):504-509.  doi:10.36849/JDD.7438.


Assuntos
Envelhecimento da Pele , Pele , Raios Ultravioleta , Envelhecimento da Pele/efeitos da radiação , Humanos , Raios Ultravioleta/efeitos adversos , Pele/efeitos da radiação , Pele/patologia , Raios Infravermelhos/efeitos adversos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/etiologia
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 857-861, 2024 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-38955733

RESUMO

Objective: To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings. Methods: The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated. Results: In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot (P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion: Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.


Assuntos
Desinfecção , Raios Ultravioleta , Desinfecção/métodos , Infecção Hospitalar/prevenção & controle
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