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1.
Hum Mol Genet ; 30(3-4): 172-181, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33480989

RESUMO

Telomere fusions lead to a state of genomic instability, and are thought to drive clonal evolution and tumorigenesis. Telomere fusions occur via both Classical and Alternative Non-Homologous End Joining repair pathways. AsiDNA is a DNA repair inhibitor that acts by mimicking a DNA double strand break (DSB) and hijacking the recruitment of proteins involved in various DNA repair pathways. In this study, we investigated whether the inhibition of DSB-repair pathways by AsiDNA could prevent telomere fusions during crisis. The present study showed that AsiDNA decreased the frequency of telomere fusions without affecting the rate of telomere erosion. Further, it indicated that AsiDNA does not impact the choice of the repair pathway used for the fusion of short dysfunctional telomeres. AsiDNA is thought to prevent short telomeres from fusing by inhibiting DNA repair. An alternative, non-mutually exclusive possibility is that cells harbouring fusions preferentially die in the presence of AsiDNA, thus resulting in a reduction in fusion frequency. This important work could open the way for investigating the use of AsiDNA in the treatment of tumours that have short dysfunctional telomeres and/or are experiencing genomic instability.


Assuntos
Reparo do DNA/efeitos dos fármacos , Encurtamento do Telômero , Telômero/metabolismo , Células HCT116 , Humanos
2.
Biotechnol Lett ; 45(4): 499-508, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738355

RESUMO

PURPOSE: We purified and characterized a novel ene-reductase (KaDBR1) from Kazachstania exigua HSC6 for the synthesis of dihydro-ß-ionone from ß-ionone. METHODS: KaDBR1 was purified to homogeneity by ammonium sulfate precipitation and phenyl-Sepharose Fast Flow and Q-Sepharose chromatography. The purified enzyme was characterized by measuring the amount of dihydro-ß-ionone from ß-ionone with LC-MS analysis method. RESULTS: The molecular mass of KaDBR1 was estimated to be 45 kDa by SDS-PAGE. The purified KaDBR1 enzyme had optimal activity at 60 °C and pH 6.0. The addition of 5 mM Mg2+, Ca2+, Al3+, Na+, and dithiothreitol increased the activity of KaDBR1 by 25%, 18%, 34%, 20%, and 23%, respectively. KaDBR1 favored NADH over NADPH as a cofactor, and its catalytic efficiency (kcat/Km) toward ß-ionone using NADH was 8.1-fold greater than when using NADPH. CONCLUSION: Owing to its unique properties, KaDBR1 is a potential candidate for the enzymatic biotransformation of ß-ionone to dihydro-ß-ionone in biotechnology applications.


Assuntos
NAD , Oxirredutases , NADP , Concentração de Íons de Hidrogênio , Peso Molecular
3.
Sensors (Basel) ; 23(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37960554

RESUMO

The paper explores the application of Steiner's most-frequent-value (MFV) statistical method in sensor data analysis. The MFV is introduced as a powerful tool to identify the most-common value in a dataset, even when data points are scattered, unlike traditional mode calculations. Furthermore, the paper underscores the MFV method's versatility in estimating environmental gamma background blue (the natural level of gamma radiation present in the environment, typically originating from natural sources such as rocks, soil, and cosmic rays), making it useful in scenarios where traditional statistical methods are challenging. It presents the MFV approach as a reliable technique for characterizing ambient radiation levels around large-scale experiments, such as the DEAP-3600 dark matter detector. Using the MFV alongside passive sensors such as thermoluminescent detectors and employing a bootstrapping approach, this study showcases its effectiveness in evaluating background radiation and its aptness for estimating confidence intervals. In summary, this paper underscores the importance of the MFV and bootstrapping as valuable statistical tools in various scientific fields that involve the analysis of sensor data. These tools help in estimating the most-common values and make data analysis easier, especially in complex situations, where we need to be reasonably confident about our estimated ranges. Our calculations based on MFV statistics and bootstrapping indicate that the ambient radiation level in Cube Hall at SNOLAB is 35.19 µGy for 1342 h of exposure, with an uncertainty range of +3.41 to -3.59µGy, corresponding to a 68.27% confidence level. In the vicinity of the DEAP-3600 water shielding, the ambient radiation level is approximately 34.80 µGy, with an uncertainty range of +3.58 to -3.48µGy, also at a 68.27% confidence level. These findings offer crucial guidance for experimental design at SNOLAB, especially in the context of dark matter research.

4.
Sensors (Basel) ; 23(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36850546

RESUMO

The paper describes a system and experimental procedure that use integrating passive detectors, such as thermoluminescent dosimeters (TLDs), for the measurement of ultra-low-level ambient dose equivalent rate values at the underground SNOLAB facility located in Sudbury, Ontario, Canada. Because these detectors are passive and can be exposed for relatively long periods of time, they can provide better sensitivity for measuring ultra-low activity levels. The final characterization of ultra-low-level ambient dose around water shielding for ongoing direct dark matter search experiments in Cube Hall at SNOLAB underground laboratory is given. The conclusion is that TLDs provide reliable results in the measurement of the ultra-low-level environmental radiation background.

5.
J Radiol Prot ; 43(3)2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37619555

RESUMO

This paper is a continuation of a study published recently by the authors. It presents and discusses computed personal absorbed dose in the lens of the eye (Dp lens/Φ), and a relative biological effectiveness (RBE)-weighted absorbed dose (in terms of an newly proposed operational quantity RBE ×Dp lens/Φ), conversion coefficients for the lens of the eye for neutron exposure at incident energies from thermal to ∼20 MeV and at angles of incidence from 0°to 90°in 15° increments, at 180° and for rotational incidence irradiation geometry (from 0°to 360°in 5°increments). These conversion coefficients were obtained from a simulation model developed for this study that contains the stylised eye model, embedded in the adult UF-ORNL mathematical phantom, whereby the previously stated RBE-weighted absorbed dose was obtained using the proposed RBE versus neutron energy distribution compiled in a previous paper by the authors. The simulations carried out for this study using the Monte Carlo N-Particle transport code version 6.2, were conducted in a realistic human eye model, for the left and right sensitive and whole volume of the lens of the eye, considering the recent proposed redefinition of the operational quantities for external radiation exposure in International Commission on Radiation Units and Measurements (ICRU) report 95. A comprehensive set of tabulated data for neutron fluence-to-dose conversion coefficients (Dp lens/Φin pGy cm2) and RBE-weighted absorbed dose (RBE ×Dp lens/Φin pGy cm2) conversion coefficients is included in this paper as a function of incident neutron energy and angle of incidence. Data forDp lens/Φ(pGy cm2) are compared to similar data from the literature for validation of our model. Data for RBE ×Dp lens/Φ(in pGy cm2), were also compared to the equivalent operational quantityHp(3,α)/Φ(in pSv cm2) conversion coefficients calculated at 3 mm depth in a cylindrical phantom for different incident neutron energies and angles of incidence from 0°to 75°in 15°increments to demonstrate the relevance of this newly proposed operational quantity for doses resulting in tissue reactions (deterministic effects) which should be quoted in Gray (RBE-weighted absorbed dose, RBE ×D(Gy)), rather than Sievert (Sv) which is reserved for stochastic effects. The current neutron weighted absorbed dose (RBE ×Dp lens) is proposed for the tissue reactions in the eye-lens for neutron radiation as per National Council on Radiation Protection and Measurements report 180 and in line with the recent proposal for the review and revision of the System of Radiological Protection to Keeping the International Commission on Radiological Protection (ICRP) recommendations fit for purpose. This method would bring better alignment between the dose limits in ICRP 118 and the new operational quantity consistent with the units of the new eye-lens dose limits without being overly conservative. The utilization of the proposed new operational quantities, as outlined in ICRU 95, has the potential to address the ongoing challenge in enforcing regulatory limits for neutron eye dose, specifically the use of Gy instead of Sv. It should be noted that the applicability of this will vary from country to country as in many countries the legislation is likely to mandate the use ofHp(3) until the regulation is amended. This approach can serve as an interim solution while awaiting the issuance of the new ICRP general recommendations, which is expected to take several years. Implementing the new operational quantities can contribute to enhancing the accuracy and effectiveness of neutron eye dose limit enforcement.


Assuntos
Cristalino , Adulto , Humanos , Incidência , Eficiência Biológica Relativa , Radiometria , Nêutrons
6.
J Radiol Prot ; 42(4)2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36538825

RESUMO

In 2012, the International Commission on Radiological Protection issued new recommendations, in publication 118, regarding the dose limits to the eye-lens. New analyses of historical exposure data had indicated that radiation-induced cataracts may appear at lower doses than previously assumed. This spurred largescale efforts in a variety of fields including dosimetry, radiation effects simulations, and the review of national regulatory limits. On the simulation side, much work led to the publication of dose rate conversion factors (DRCFs), to calculate the dose to the radiosensitive part of the eye-lens, and to the whole eye-lens as functions of the incident fluence of electron, photon, positron, and neutron radiation. The standard, ISO-15382 (2015Radiological Protection-Procedures for Monitoring the Dose to the Lens of the Eye, the Skin and the Extremities), from the International Organization for Standardization (ISO), stated that the direct contact of a hot radioactive particle on the eye-lens represents a special contamination condition that must be considered. The aim of this work was to produce tabulated data of eye-lens dose rates, per activity (MBq), for a variety of radionuclides. In this work, the dose to the eye-lens from contamination directly in contact with the cornea, expressed in terms of DRCFs for eye-lens, in units of Gy h-1MBq-1, are presented for 102 radionuclides of interest. These radionuclides were selected as they had been considered by the International Atomic Energy Agency of importance for skin dose. The method consisted of two steps. The first was the determination of the DRCFs for mono-energetic electrons and photons for a hot particle in contact with the eye-lens, followed by the folding of these quantities with the emissions of the radionuclides of interest. Contributions from spontaneous fission neutrons were considered separately. Exposure geometries for spherical hot particles of different dimensions, materials and locations on the cornea were considered. In addition, partial surface coverage of the cornea, consistent with an accidental exposure to a contaminated liquid, was also modelled. Resulting radionuclide DRCFs were verified, for a few specific geometries and radionuclides with dedicated Monte Carlo simulations. The final data are presented in several tables included in this paper.


Assuntos
Cristalino , Lesões por Radiação , Humanos , Doses de Radiação , Radiometria/métodos , Radioisótopos , Cristalino/efeitos da radiação , Córnea , Método de Monte Carlo
7.
Int J Cosmet Sci ; 44(1): 91-102, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34860432

RESUMO

OBJECTIVE: This study was initiated and conducted by several laboratories, 3 of the main cosmetic ingredient suppliers and 4 brands of cosmetics in France. Its objective is to show the interest and robustness of coupling chemical and genetic analyses in the identification of plant species. In this study, the Lavandula genus was used. METHODS: In this study, we used two analytical methods. Chemical analysis from UHPLC (ultra-high-performance liquid chromatography) and genetic analysis from barcoding with genetic markers. RESULTS: Eleven lavender species were selected (botanically authenticated) and analysed. The results show that three chemical compounds (coumaric acid hexoside, ferulic acid hexoside and rosmarinic acid) and three genetic markers (RbcL, trnH-psbA and ITS) are of interest for the differentiation of species of the genus lavandula. CONCLUSION: The results show that the combination of complementary analytical methods is a relevant system to prove the botanical identification of lavender species. This first study, carried out on a plant of interest for cosmetics, demonstrates the need for authentication using a tool combining genetic and chemical analysis as an advance over traditional investigation methods used alone, in terms of identification and authentication reliability.


OBJECTIF: Cette étude a été lancée et menée par plusieurs laboratoires, trois des principaux fournisseurs d'ingrédients cosmétiques et quatre marques de cosmétiques en France. Son objectif est de montrer qu'associer les analyses chimiques et génétiques dans l'identification des espèces végétales présente un intérêt et est une approche solide. Dans cette étude, c'est le genre Lavandula qui a été utilisé. MÉTHODES: Dans cette étude, nous avons fait appel à deux méthodes analytiques. L'analyse chimique, à partir de la chromatographie en phase liquide à haute performance (ultra-high-performance liquid chromatography, UHPLC), et l'analyse génétique en procédant à un codage à barres avec des marqueurs génétiques. RÉSULTATS: Onze espèces de lavande ont été sélectionnées (authentifiées du point de vue botanique) et analysées. Les résultats montrent que trois composés chimiques (acide coumarique hexoside, acide ferulique hexoside et acide rosmarinique) et trois marqueurs génétiques (RbcL, trnH-psbA et ITS) présentent un intérêt pour la différenciation des espèces du genre lavandula. CONCLUSION: Les résultats montrent que la combinaison de méthodes analytiques complémentaires est un système pertinent pour prouver l'identification végétale des espèces de lavande. Cette première étude, réalisée sur une plante qui offre un intérêt pour les cosmétiques, démontre la nécessité de procéder à une authentification à l'aide d'un outil qui conjugue analyse génétique et chimique ; elle représente une avancée par rapport aux méthodes d'investigation traditionnelles utilisées seules, en termes d'identification et de fiabilité de l'authentification.


Assuntos
Código de Barras de DNA Taxonômico , Lavandula , Código de Barras de DNA Taxonômico/métodos , DNA de Plantas/genética , Marcadores Genéticos , Lavandula/genética , Reprodutibilidade dos Testes
8.
J Radiol Prot ; 42(3)2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36070675

RESUMO

For planned occupational exposure situations, the International Commission on Radiological Protection (ICRP) publication 118 recommends an equivalent dose limit for the lens of the eye of 20 mSv yr-1averaged over 5 yr with no single year exceeding 50 mSv. Regulatory authorities of various jurisdictions worldwide followed some or all, of the ICRP recommendations and implemented reduced occupational lens of eye dose limits in their legislation. As compliance with the eye-lens dose limit will be based on the summation of doses received from all types of radiation, applicable to a variety of workplaces, the contribution of neutrons to eye lens dose will be important where it contributes a significant fraction of the total dose to the eye lens. This work presents and discusses computed personal absorbed dose (Dlens/Φ), and personal dose equivalent (Hp(3)/Φ) as well as a newly proposed relative biological effectiveness (RBE)-weighted absorbed dose (RBE ×Dlens/Φ) conversion coefficients for the lens of the eye for neutron exposure at incident energies from thermal to ∼20 MeV. TheDlens/Φ coefficients were obtained from a simulation model developed for this study that contains the stylised eye model embedded in the adult UF-ORNL mathematical phantom. The modelling techniques used in these simulations were also used to calculateHp(3)/Φ for the International Commission on Radiation Units and Measurements (ICRU) slab and cylinder phantoms. All simulations carried out for this study utilised the Monte Carlo N-Particle (MCNP) series of codes. The results are compared with the related published data. The issue of compliance with the current equivalent dose limit for the lens of the eye is addressed from a neutron perspective considering the recent proposed redefinition of the operational quantities for external radiation exposure in ICRU report 95. The use of a radiation weighted absorbed dose (RBE ×Dlens, in Gy) is proposed for the tissue reactions in the eye-lens for neutron radiation as per the National Council on Radiation Protection and Measurements report 180, and in line with the recent review and revision of the System of Radiological Protection To Keeping the ICRP Recommendations Fit for Purpose, which states that RBE weighted dose should be used for high-Linear energy transfer (LET) radiations such as neutrons. This confirms the earlier statement in ICRP publication 92, paragraph 297 and reiterated in the Executive summary, paragraph (q) of ICRP publication 118. The proposed approach would provide an operational quantity consistent with the units of the new eye-lens dose limits without being overly conservative.


Assuntos
Cristalino , Proteção Radiológica , Método de Monte Carlo , Nêutrons , Doses de Radiação , Proteção Radiológica/métodos , Radiometria/métodos
9.
J Radiol Prot ; 42(1)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34715681

RESUMO

For occupational exposures in planned exposure situations International Commission on Radiological Protection (ICRP) publication 118 recommends an equivalent dose limit for the lens of the eye of 20 mSv yr-1averaged over five years with no single year exceeding 50 mSv. This constitutes a reduction from the previous limit of 150 mSv yr-1. The Canadian nuclear regulator, the Canadian Nuclear Safety Commission, responded to the ICRP recommendation by initiating amendments to theRadiation Protection Regulationsthrough a discussion paper which was published for comment by interested stakeholders in 2013. The revised equivalent dose limit of 50 mSv in a one-year dosimetry period for nuclear energy workers came into effect in January 2021. This paper presents the outcome of discussions with Canadian stakeholders in diverse fields of radiological work which focused on the implementation of the reduced occupational equivalent dose limit for the lens of the eye in their respective workplaces. These exchanges highlighted the existing practices for monitoring doses to the lens of the eye and identified current technological gaps. The exchanges also identified that, in many cases, the lens of the eye dose is anticipated to be well within the new dose limit despite some of the gaps in technology. The paper also presents the monitoring and eye-lens dose assessment solutions that are available based on different methods for eye-lens monitoring; presented together with criteria for their use.


Assuntos
Cristalino , Exposição Ocupacional , Proteção Radiológica , Canadá , Humanos , Doses de Radiação , Radiometria
10.
Biotechnol Lett ; 43(12): 2233-2241, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34618272

RESUMO

To characterize a novel thermophilic ß-carotene 15,15'-monooxygenase BCMO7211 isolated from the marine bacterium Candidatus Pelagibacter sp. HTCC7211. BCMO7211 was functionally overexpressed in Escherichia coli and purified to homogeneity by Ni-NTA affinity chromatography and Superdex-200 gel filtration chromatography. Labeling experiments with H218O demonstrated that the oxygen atom in the terminal aldehyde group of the produced retinal molecules was provided from both molecular oxygen and water, indicating that BCMO7211 is the first characterized bacterial ß-carotene 15,15'-monooxygenase. BCMO7211 exhibited broad carotenoid substrate specificity toward α-carotene, ß-cryptoxanthin, ß-carotene, zeaxanthin, and lutein. The optimum temperature, pH, and concentrations of the substrate and enzyme for retinal production were 60 °C, 9.0, 500 mg ß-carotene/L, and 2.5 U/ml, respectively. Under optimum conditions, 888.3 mg/L retinal was produced in 60 min with a conversion rate of 89.0% (w/w). BCMO7211 is a potential candidate for the enzymatic synthesis of retinal in biotechnological applications.


Assuntos
Organismos Aquáticos/enzimologia , Inibidores Enzimáticos/farmacologia , Rhizobiaceae/enzimologia , beta-Caroteno 15,15'-Mono-Oxigenase/química , Escherichia coli/genética , Especificidade por Substrato/genética , beta-Caroteno 15,15'-Mono-Oxigenase/antagonistas & inibidores , beta-Caroteno 15,15'-Mono-Oxigenase/genética , beta-Caroteno 15,15'-Mono-Oxigenase/isolamento & purificação
11.
Molecules ; 23(2)2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29414844

RESUMO

To develop natural product resources to control cigarette beetles (Lasioderma serricorne), the essential oil from Artemisia lavandulaefolia (Compositae) was investigated. Oil was extracted by hydrodistillation of the above-ground portion of A. lavandulaefolia and analyzed using gas chromatography-mass spectrometer (GC-MS). Extracted essential oil and three compounds isolated from the oil were then evaluated in laboratory assays to determine the fumigant, contact, and repellent efficacy against the stored-products' pest, L. serricorne. The bioactive constituents from the oil extracts were identified as chamazulene (40.4%), 1,8-cineole (16.0%), and ß-caryophyllene (11.5%). In the insecticidal activity assay, the adults of L. serricorne were susceptible to fumigant action of the essential oil and 1,8-cineole, with LC50 values of 31.81 and 5.18 mg/L air. The essential oil, 1,8-cineole, chamazulene, and ß-caryophyllene exhibited contact toxicity with LD50 values of 13.51, 15.58, 15.18 and 35.52 µg/adult, respectively. During the repellency test, the essential oil and chamazulene had repellency approximating the positive control. The results indicated that chamazulene was abundant in A. lavandulaefolia essential oil and was toxic to cigarette beetles.


Assuntos
Artemisia/química , Besouros/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Inseticidas/química , Inseticidas/farmacologia , Estrutura Molecular , Óleos Voláteis/isolamento & purificação , Compostos Fitoquímicos/química , Extratos Vegetais/isolamento & purificação
12.
Eur Radiol ; 27(10): 4435-4444, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28374075

RESUMO

OBJECTIVE: This study aimed to explore the antitumour effect of the DNA repair inhibitor, DT01 (the cholesterol conjugated form of Dbait), as an adjunct treatment to enhance the therapeutic efficacy of transarterial chemoembolization (TACE) in pre-clinical models of hepatocellular carcinoma (HCC). METHODS: A rabbit model bearing liver tumours was either left untreated or treated with TACE or with a combination of TACE+DT01. Tumour growth was monitored by ultrasound. These results were further confirmed in mice grafted with an intrahepatic human HCC model treated with doxorubicin (DOX) alone or DOX+DT01. RESULTS: The combination of DT01 with TACE in a rabbit liver model led to a significant decrease in tumour volume (p=0.03). Colour Doppler and immunohistochemical staining revealed a strong decrease in vascularization in the DT01+TACE-treated group preventing the tumour growth restart observed after TACE alone. Similarly, the DT01 combination with DOX led to significant anti-tumour efficacy compared to DOX alone (p=0.02) in the human HCC model. In addition, a significant decrease in vascularization in the group receiving combination DT01 and DOX treatment was observed. CONCLUSIONS: DT01 is well tolerated and may potentiate HCC treatment by enhancing the DNA-damaging and anti-vascularization effect of TACE with doxorubicin. KEY POINTS: • DT01 combined with TACE leads to significant anti-tumour efficacy without additional toxicity. • A potential anti-angiogenic role of DT01 was identified in preclinical models. • DT01 may potentiate HCC treatment by enhancing the efficacy of TACE.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Colesterol/análogos & derivados , Reparo do DNA/efeitos dos fármacos , DNA/uso terapêutico , Doxorrubicina/uso terapêutico , Neoplasias Hepáticas/terapia , Animais , Carcinoma Hepatocelular/genética , Quimioembolização Terapêutica/métodos , Colesterol/uso terapêutico , Dano ao DNA , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/genética , Masculino , Coelhos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
13.
Nucleic Acids Res ; 41(15): 7344-55, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23761435

RESUMO

One of the major early steps of repair is the recruitment of repair proteins at the damage site, and this is coordinated by a cascade of modifications controlled by phosphatidylinositol 3-kinase-related kinases and/or poly (ADP-ribose) polymerase (PARP). We used short interfering DNA molecules mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) to promote DNA-dependent protein kinase (DNA-PK) and PARP activation. Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. Therefore, comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both recruit proteins involved in single-strand break repair (PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break repair (53BP1, NBS1, RAD51 and DNA-PK). By these ways, Pbait and Dbait disorganize DNA repair, thereby sensitizing cells to various treatments. Single-strand breaks repair inhibition depends on direct trapping of the main proteins on both molecules. Double-strand breaks repair inhibition may be indirect, resulting from the phosphorylation of double-strand breaks repair proteins and chromatin targets by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations.


Assuntos
Dano ao DNA , Reparo do DNA , Proteína Quinase Ativada por DNA/metabolismo , Proteínas Nucleares/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Sequência de Bases , Benzimidazóis/farmacologia , Quebras de DNA de Cadeia Dupla , Proteína Quinase Ativada por DNA/genética , Ativação Enzimática , Genoma Humano , Células HeLa , Humanos , Proteínas Nucleares/genética , Fosforilação , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Poli(ADP-Ribose) Polimerases/genética
14.
Molecules ; 20(12): 21939-45, 2015 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-26670226

RESUMO

The essential oil obtained by hydrodistillation from Alpinia kwangsiensis rhizomes was investigated by GC-MS. A total of 31 components representing 92.45% of the oil were identified and the main compounds in the oil were found to be camphor (17.59%), eucalyptol (15.16%), ß-pinene (11.15%) and α-pinene (10.50%). These four compounds were subsequently isolated and the essential oil and four isolated compounds exhibited potent insecticidal activity against Lasioderma serricorne adults. During the assay, it was shown that the essential oil exhibited both potential contact (LD50 = of 24.59 µg/adult) and fumigant (LC50 = of 9.91 mg/L air) toxicity against Lasioderma serricorne. The study revealed that the insecticidal activity of the essential oil can be attributed to the synergistic effects of its diverse major components, which indicates that oil of Alpinia kwangsiensis and its isolated compounds have potential to be developed into natural insecticides to control insects in stored grains and traditional Chinese medicinal materials.


Assuntos
Alpinia/química , Besouros/efeitos dos fármacos , Inseticidas/química , Inseticidas/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Rizoma/química , Animais , Cromatografia Gasosa-Espectrometria de Massas , Inseticidas/isolamento & purificação , Óleos Voláteis/isolamento & purificação
15.
Radiology ; 270(3): 736-46, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24475822

RESUMO

PURPOSE: To assess the usefulness of combining hyperthermia with a DNA repair inhibitor (double-strand break bait [Dbait]) and its potential application to radiofrequency ablation (RFA) in a preclinical model of human colorectal cancer. MATERIALS AND METHODS: The local ethics committee of animal experimentation approved all investigations. First, the relevance was assessed by studying the survival of four human colorectal adenocarcinoma cell cultures after 1 hour of hyperthermia at 41°C or 43°C with or without Dbait. Human colon adenocarcinoma cells (HT-29) were grafted subcutaneously into nude mice (n = 111). When tumors reached approximately 500 mm(3), mice were treated with Dbait alone (n = 20), sublethal RFA (n = 21), three different Dbait schemes and sublethal RFA (n = 52), or a sham treatment (n = 18). RFA was performed to ablate the tumor center alone. To elucidate antitumor mechanisms, 39 mice were sacrificed for blinded pathologic analysis, including assessment of DNA damage, cell proliferation, and tumor necrosis. Others were monitored for tumor growth and survival. Analyses of variance and log-rank tests were used to evaluate differences. RESULTS: When associated with mild hyperthermia, Dbait induced cytotoxicity in all tested colon cancer cell lines. Sublethal RFA or Dbait treatment alone moderately improved survival (median, 40 days vs 28 days for control; P = .0005) but combination treatment significantly improved survival (median, 84 days vs 40 days for RFA alone, P = .0004), with approximately half of the animals showing complete tumor responses. Pathologic studies showed that the Dbait and RFA combination strongly enhances DNA damage and coagulation areas in tumors. CONCLUSION: Combining Dbait with RFA sensitizes the tumor periphery to mild hyperthermia and increases RFA antitumor efficacy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Ablação por Cateter , Neoplasias Colorretais/patologia , Reparo do DNA/efeitos dos fármacos , Hipertermia Induzida , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Oligodesoxirribonucleotídeos/farmacologia , Adenocarcinoma/patologia , Animais , Dano ao DNA/efeitos dos fármacos , Humanos , Camundongos , Células Tumorais Cultivadas
16.
Health Phys ; 126(5): 339-345, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38526252

RESUMO

ABSTRACT: After considering epidemiological studies on the induction of cataracts in individuals exposed to radiation, the International Commission on Radiological Protection recommended, in 2012, a reduction in the annual eye-dose limit of occupationally exposed workers. This imposed higher performance demands on existing dosimetry systems and the development of new dosimetry technologies. The operational quantity to be measured is Hp(3), the personal dose equivalent at a depth of 3 mm in an ICRU 4-element tissue cylinder 20 cm in height and 20 cm in diameter. The conversion coefficients per unit incident fluence, Hp(3)/Φ, were calculated using Monte Carlo simulation codes. In the case of incident electrons, the literature shows that the resulting coefficients depend on the electron transport options selected for the Monte Carlo simulations as well as the tally zone thickness. In this study, electron operational eye-lens dose coefficients were calculated using MCNP6.2 in its default settings and by invoking the single-event feature. The results were compared to those from PENELOPE, a well-known code for its enhanced accuracy in handling low-energy electron transport. The results are in agreement for the entire energy range for these two series of simulations, but differences are found with previously published dose coefficients in the literature. This impacts the calibration of dosimeters for electrons and may require a change in the commonly accepted dose coefficients.


Assuntos
Catarata , Cristalino , Humanos , Elétrons , Método de Monte Carlo , Calibragem
17.
Biomimetics (Basel) ; 9(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38392109

RESUMO

Successful bioinspired design depends on practitioners' access to biological data in a relevant form. Although multiple open-access biodiversity databases exist, their presentation is often adapted to life scientists, rather than bioinspired designers. In this paper, we present a new tool, "Bioinspire-Explore", for navigating biodiversity data in order to uncover biological systems of interest for a range of sectors. Bioinspire-Explore allows users to search for inspiring biological models via taxa (species, genera, etc.) as an entry point. It provides information on a taxon's position in the "tree of life", its distribution and climatic niche, as well as its appearance. Bioinspire-Explore also shows users connections in the bioinspiration literature between their taxon of interest and associated biological processes, habitats, and physical measurements by way of their semantic proximity. We believe Bioinspire-Explore has the potential to become an indispensable resource for both biologists and bioinspired designers in different fields.

18.
J Biol Chem ; 287(12): 8803-15, 2012 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-22270370

RESUMO

DNA damage triggers a complex signaling cascade involving a multitude of phosphorylation events. We found that the threonine 7 (Thr-7) residue of heat shock protein 90α (Hsp90α) was phosphorylated immediately after DNA damage. The phosphorylated Hsp90α then accumulated at sites of DNA double strand breaks and formed repair foci with slow kinetics, matching the repair kinetics of complex DNA damage. The phosphorylation of Hsp90α was dependent on phosphatidylinositol 3-kinase-like kinases, including the DNA-dependent protein kinase (DNA-PK) in particular. DNA-PK plays an essential role in the repair of DNA double strand breaks by nonhomologous end-joining and in the signaling of DNA damage. It is also present in the cytoplasm of the cell and has been suggested to play a role in cytoplasmic signaling pathways. Using stabilized double-stranded DNA molecules to activate DNA-PK, we showed that an active DNA-PK complex could be assembled in the cytoplasm, resulting in phosphorylation of the cytoplasmic pool of Hsp90α. In vivo, reverse phase protein array data for tumors revealed that basal levels of Thr-7-phosphorylated Hsp90α were correlated with phosphorylated histone H2AX levels. The Thr-7 phosphorylation of the ubiquitously produced and secreted Hsp90α may therefore serve as a surrogate biomarker of DNA damage. These findings shed light on the interplay between central DNA repair enzymes and an essential molecular chaperone.


Assuntos
Dano ao DNA , Reparo do DNA , Proteínas de Choque Térmico HSP90/metabolismo , Motivos de Aminoácidos , Animais , Linhagem Celular Tumoral , Feminino , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/genética , Humanos , Camundongos , Camundongos Nus , Fosforilação , Ratos
19.
Health Phys ; 125(5): 383-392, 2023 11 01.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-37650737

RESUMO

ABSTRACT: In the last decade, the International Commission on Radiological Protection recommended a reduction in the annual limits to the dose to the lens of the eye from 150 mSv to 20 mSv y -1 , averaged over defined periods of 5 y, with no single year exceeding 50 mSv. To assist the health physics community in this task, many groups have calculated protection and operational fluence dose coefficients. This led to the publication of multiple coefficient tables that were calculated for arrays of different parameters, including particle type, angle of incidence, target phantom models, presence or absence of secondary charged particle equilibrium, etc. The coefficients available in the literature include protection dose values calculated in a realistic eye model and operational values calculated in a simplified cylindrical head phantom at a point 3 mm below the surface. This paper reports on a simple Windows™ application that was written to aid health physics professionals in accessing and using the large body of available protection and operational eye-lens data. The application is called the Eye-Lens Dose Calculator, as it also performs calculations of the eye-lens dose for radionuclides, where the complete emissions of the selected radionuclides are considered. Test cases show that there is good agreement between the calculated protection and operational dose quantities when radionuclide emission characteristics are considered.


Assuntos
Cristalino , Radiometria , Humanos , Física Médica , Pessoal de Saúde , Software
20.
Radiat Prot Dosimetry ; 199(7): 660-669, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37005861

RESUMO

At radiological facilities, protocols are in place to guide radiation protection personnel in the event of the radioactive contamination of surfaces. A count rate measurement is performed with a portable contamination survey meter and a sample of the contamination is taken for later analysis and identification of the radionuclides. If the contaminated surface was of a worker's skin, then a skin dose assessment is made. The determination of the absolute activity of the radionuclides of the contamination often rests on the assumed detection efficiency of the survey meter used in the initial counting. This may lead to important underestimation or overestimation of the radionuclides' activities as the detection efficiency of the instrument must depend on the radiation type, the energy and the backscatter characteristics of the surface. This paper reports on a user-friendly computer application that relies on databases of pre-calculated detection efficiencies and skin dose rate conversion factors for the accurate assessment of contamination activities and skin doses. The results of some cases are compared with the available data in the literature.


Assuntos
Monitoramento de Radiação , Proteção Radiológica , Software , Pele , Radioisótopos/análise , Doses de Radiação , Monitoramento de Radiação/métodos
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