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1.
Nat Commun ; 12(1): 5530, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545083

RESUMO

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Amplificação de Genes , Glioma/genética , Recidiva Local de Neoplasia/patologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Adolescente , Adulto , Criança , Deleção Cromossômica , Análise por Conglomerados , Metilação de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Rearranjo Gênico/genética , Genoma Humano , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Radiação , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transcrição Genética , Adulto Jovem
2.
Nat Commun ; 12(1): 5531, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545084

RESUMO

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.


Assuntos
Glioma/genética , Glioma/patologia , Radiação , Adolescente , Criança , Estudos de Coortes , Simulação por Computador , Variações do Número de Cópias de DNA/genética , Metilação de DNA/genética , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Gradação de Tumores , Transcriptoma/genética , Adulto Jovem
3.
J Immunol ; 207(7): 1812-1823, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34462312

RESUMO

Radiation is associated with tissue damage and increased risk of atherosclerosis, but there are currently no treatments and a very limited mechanistic understanding of how radiation impacts tissue repair mechanisms. We uncovered that radiation significantly delayed temporal resolution programs that were associated with decreased efferocytosis in vivo. Resolvin D1 (RvD1), a known proresolving ligand, promoted swift resolution and restored efferocytosis in sublethally irradiated mice. Irradiated macrophages exhibited several features of senescence, including increased expression of p16INK4A and p21, heightened levels of SA-ß-gal, COX-2, several proinflammatory cytokines/chemokines, and oxidative stress (OS) in vitro, and when transferred to mice, they exacerbated inflammation in vivo. Mechanistically, heightened OS in senescent macrophages led to impairment in their ability to carry out efficient efferocytosis, and treatment with RvD1 reduced OS and improved efferocytosis. Sublethally irradiated Ldlr -/- mice exhibited increased plaque necrosis, p16INK4A cells, and decreased lesional collagen compared with nonirradiated controls, and treatment with RvD1 significantly reduced necrosis and increased lesional collagen. Removal of p16INK4A hematopoietic cells during advanced atherosclerosis with p16-3MR mice reduced plaque necrosis and increased production of key intraplaque-resolving mediators. Our results demonstrate that sublethal radiation drives macrophage senescence and efferocytosis defects and suggest that RvD1 may be a new therapeutic strategy to limit radiation-induced tissue damage.


Assuntos
Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Ácidos Docosa-Hexaenoicos/metabolismo , Células-Tronco Hematopoéticas/fisiologia , Macrófagos/imunologia , Lesões por Radiação/imunologia , Cicatrização/efeitos da radiação , Animais , Aterosclerose/genética , Células Cultivadas , Senescência Celular , Ciclo-Oxigenase 2/metabolismo , Genes p16 , Humanos , Inflamação , Camundongos , Camundongos Knockout , Radiação
4.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066508

RESUMO

Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5'-Aminolevulinic acid (5'-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Neoplasias Ovarianas/terapia , Fotoquimioterapia , Radiação , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linhagem Celular Tumoral , Feminino , Injeções Intraperitoneais , Camundongos Endogâmicos BALB C
5.
Carbohydr Polym ; 265: 118037, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33966824

RESUMO

Electron beam irradiation (EBI) is an alternative treatment for intrinsic viscosity (IV) control in cellulose pulps, but has never been integrated in full bleaching sequences for comparison to conventional methods. Both eucalyptus kraft (EK) paper pulp and beech sulfite (BS) dissolving pulp were subjected to totally chlorine free (TCF) bleaching sequences comprising either EBI, ozone, or both for IV control. Additionally, effects of EBI on hexenuronic acid (HexA) and xylan were investigated. IV was adjusted to 450-500 mL g-1 and properties including carbonyl content, kappa, brightness, alkali-resistance and sugar composition were compared. Pulps produced with EBI had a higher alkali-resistance, uniformity and less cellulose oxidation. However, the degree of bleaching (DoB) was low without the use of ozone. HexA content in a birch pulp was halved by EBI. Isolated xylans were more resistant to irradiation than cellulose with little decrease of molar masses and moderate oxidation.


Assuntos
Celulose/química , Eucalyptus/química , Fagus/química , Ozônio/química , Álcalis/química , Clareadores/química , Elétrons , Ácidos Hexurônicos/química , Lignina/química , Oxirredução , Papel , Radiação , Viscosidade , Xilanos/química
6.
J Radiat Res ; 62(Supplement_1): i53-i63, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33978171

RESUMO

Following the development of genome editing technology, it has become more feasible to create genetically modified animals such as knockout (KO), knock-in, and point-mutated animals. The genome-edited animals are useful to investigate the roles of various functional genes in many fields of biological science including radiation research. Nevertheless, some researchers may experience difficulty in generating genome-edited animals, probably due to the requirement for equipment and techniques for embryo manipulation and handling. Furthermore, after obtaining F0 generation, genome-edited animals generally need to be expanded and maintained for analyzing the target gene function. To investigate genes essential for normal birth and growth, the generation of conditional KO (cKO) animals in which a tissue- or stage-specific gene mutation can be introduced is often required. Here, we describe the basic principle and application of genome editing technology including zinc-finger nuclease, transcription-activator-like effector nuclease, and clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein (Cas) systems. Recently advanced developmental biology methods have enabled application of the technology, especially CRISPR/Cas, to zygotes, leading to the prompt production of genome-edited animals. For pre-implantation embryos, genome editing via oviductal nucleic acid delivery has been developed as an embryo manipulation- or handling-free method. Examining the gene function at F0 generation is becoming possible by employing triple-target CRISPR technology. This technology, in combination with a blastocyst complementation method enables investigation of even birth- and growth-responsible genes without establishing cKO strains. We hope that this review is helpful for understanding and expanding genome editing-related technology and for progressing radiation research.


Assuntos
Biologia do Desenvolvimento , Edição de Genes , Radiação , Pesquisa , Animais , Sistemas CRISPR-Cas/genética , Genoma , Humanos
8.
Int J Food Sci Nutr ; 72(8): 1057-1070, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33820498

RESUMO

This study investigated the effects of feeding paraprobiotics obtained by six processes [heat, ultrasound, high pH, low pH, irradiation and supercritical carbon dioxide (CO2)] on biochemical parameters and intestinal microbiota of Wistar male rats. Daily administration of paraprobiotics did not affect (p ≥ 0.05) the food intake, body weight, glucose and triglycerides levels, expression of antioxidant enzymes or thermal shock proteins in comparison to the control. Bifidobacterium lactis inactivated by irradiation and supercritical CO2 decreased the total cholesterol levels in serum (p < 0.05). Bifidobacterium lactis inactivated by supercritical CO2 increased the albumin and creatinine levels, while decreased the HDL-cholesterol levels (p < 0.05). Clostridiales (45.6-56%), Bacteroidales (31.9-44.2%) and Lactobacillales (3.9-7.8%) corresponded to the major orders in paraprobiotic groups. The properties of paraprobiotics are dependent on the method of inactivation, the intensity of the method employed and on the strain used.


Assuntos
Microbioma Gastrointestinal , Probióticos , Animais , Peso Corporal , Dióxido de Carbono , Colesterol/sangue , Temperatura Alta , Concentração de Íons de Hidrogênio , Masculino , Radiação , Ratos , Ratos Wistar
9.
Molecules ; 26(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921448

RESUMO

The evolution of different antimicrobial drugs in terrestrial, microgravity and hypergravity conditions is presented within this review, in connection with their implementation during human space exploration. Drug stability is of utmost importance for applications in outer space. Instabilities may be radiation-induced or micro-/hypergravity produced. The antimicrobial agents used in space may have diminished effects not only due to the microgravity-induced weakened immune response of astronauts, but also due to the gravity and radiation-altered pathogens. In this context, the paper provides schemes and procedures to find reliable ways of fighting multiple drug resistance acquired by microorganisms. It shows that the role of multipurpose medicines modified at the molecular scale by optical methods in long-term space missions should be considered in more detail. Solutions to maintain drug stability, even in extreme environmental conditions, are also discussed, such as those that would be encountered during long-duration space exploratory missions. While the microgravity conditions may not be avoided in space, the suggested approaches deal with the radiation-induced modifications in humans, bacteria and medicines onboard, which may be fought by novel pharmaceutical formulation strategies along with radioprotective packaging and storage.


Assuntos
Anti-Infecciosos/química , Gravitação , Radiação , Voo Espacial , Bactérias/patogenicidade , Farmacorresistência Bacteriana , Humanos , Astronave
10.
Neuroscience ; 463: 204-215, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33838288

RESUMO

Radiation-induced cognitive dysfunction is a common complication associated with cranial radiation therapy. Inhibition of hippocampal neurogenesis and proliferation plays a critical role in this complication. Relieving hippocampal apoptosis may significantly protect hippocampal neurogenesis and proliferation. Previous studies have demonstrated that hyperactivity of cyclin-dependent kinase 5 (Cdk5) is closely related to apoptosis. The exact molecular changes and function of Cdk5 in radiation-induced cognitive dysfunction are still not clear. Whether inhibition of Cdk5 and the relevant caspase-3 could improve hippocampal neurogenesis and ameliorate radiation-induced cognitive dysfunction needs further exploration. We hypothesized that inhibition of the Cdk5/caspase-3 pathway by p5-TAT could protect hippocampal neurogenesis and alleviate radiation-induced cognitive dysfunction. In our study, we reported that radiation induced hyperactivity of Cdk5 accompanied by elevation of the levels of cleaved caspase-3, a marker of neuronal apoptosis. Inhibition of hippocampal neurogenesis and proliferation as well as cognitive dysfunction was also observed. p5-TAT, a specific inhibitor of Cdk5, decreased the overactivation of Cdk5 without affecting the levels of Cdk5 activators. Additionally, this treatment suppressed the expression of cleaved caspase-3. We further demonstrated that p5-TAT treatment reduced hippocampal dysfunction and improved behavioral performance. Therefore, Cdk5 inhibition by the small peptide p5-TAT is a promising therapeutic strategy for radiation-induced cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Quinase 5 Dependente de Ciclina , Radiação , Caspase 3/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Quinase 5 Dependente de Ciclina/metabolismo , Hipocampo/metabolismo , Humanos , Neurogênese
11.
Oncol. (Guayaquil) ; 31(1): 1-7, Abril 30, 2021.
Artigo em Espanhol | LILACS | ID: biblio-1222455

RESUMO

Introducción: El hipofraccionamiento moderado (hRt) en cáncer de próstata, consisten en dismi-nuir el tiempo total de tratamiento con radioterapia, lo que mejora la adherencia terapéutica y opti-miza recursos tecnológicos. En cáncer de próstata, existe evidencia robusta con datos maduros a 5 años de seguimiento, donde se evidenció que hRtno es inferior al tratamiento con fraccionamiento estándar en control oncológico, con menor o igual toxicidad aguda y tardía. Se hace una revisión de la evidencia, dosis de tolerancia, contorneo de volúmenes objetivo (GTV-CTV-PTV) / órganos de ries-go, planificación y reproducibilidad del hRt en cáncer de próstata localizado.


Introduction: Moderate hypofractionation (hRt) in prostate cancer consists of reducing the total time of treatment with radiotherapy, which improves therapeutic adherence and optimizes technolog-ical resources. In prostate cancer, there is robust evidence with mature data at 5 years of follow-up, where it was evidenced that hRt is not inferior to treatment with standard fractionation in oncological control, with less or equal acute and late toxicity. A review of the evidence, tolerance dose, contouring of target volumes (GTV-CTV-PTV) / organs at risk, planning and reproducibility of hRt in localized prostate cancer is made.


Assuntos
Neoplasias da Próstata , Radioterapia , Hipofracionamento da Dose de Radiação , Radiação , Dosagem
12.
Oxid Med Cell Longev ; 2021: 6646323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628370

RESUMO

Objectives: Radiotherapy is a common therapy in head and neck tumors, which may cause a side effect radiation bone injury (RBI). Furthermore, it has been investigated that microRNA (miRNA) expression levels were altered after radiotherapy. Exosomes play a role in bone formation as miRNA containers, while radiation affects exosomes composition, secretion, and function. So, our objective is to explore changes in miRNA levels during bone formation after radiotherapy and identify the differentially expressed miRNAs (DE-miRs) in plasma exosomes during the process of osteogenesis related to irradiation. Materials and Methods: In this study, we analyzed nine samples from three rabbits exposed twice to radiation (15 Gy each) and detected DE-miRs from irradiated plasma exosomes during the process of osteogenesis by RNA sequencing. Further, we identified DE-miRs with significant differences and predicted their target genes via the bioinformatics analysis tools Targetscan v7.2 and miRPathDB v2.0. Finally, we identified radiation-responsive miRNAs and predicted their target genes during osteogenesis. Results: Taken together, we have identified some DE-miRs in irradiated plasma exosomes, which were involved in several vital signaling pathways related to bone physiology, such as the Wnt pathway, MAPK cascade, and calcium modulating pathway. Conclusions: We have found that plasma exosomes are one of the ways by which radiation can affect bone metabolism and regeneration. However, the specific mechanisms of how these plasma exosomal miRNAs mediate the osteogenesis pathways must be further investigated. Clinical Relevance. Radiotherapy may cause radiation bone injury, and miRNA expression levels in rabbit plasma exosomes are altered after radiotherapy. High-throughput RNA sequencing can identify the differentially expressed miRNAs in irradiated plasma exosomes during the process of osteogenesis. These findings make sense to develop novel therapeutic strategies for treating radiation-induced bone injury disorders.


Assuntos
Exossomos/genética , Exossomos/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , MicroRNAs/sangue , MicroRNAs/genética , Osteogênese/genética , Osteogênese/efeitos da radiação , Radiação , Animais , Perfilação da Expressão Gênica , Masculino , Coelhos , Reprodutibilidade dos Testes
13.
Cells ; 10(1)2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445526

RESUMO

The current treatment strategy for patients with aggressive colorectal cancer has been hampered by resistance to radiotherapy and chemotherapy due to the existence of cancer stem-like cells (CSCs). Recent studies have shown that SOX2 expression plays an important role in the maintenance of CSC properties in colorectal cancer. In this study, we investigated the induction and regulatory role of SOX2 following the irradiation of radioresistant and radiosensitive colorectal cancer cells. We used FACS and western blotting to analyze SOX2 expression in cells. Among the markers of colorectal CSCs, the expression of CD44 increased upon irradiation in radioresistant cells. Further analysis revealed the retention of CSC properties with an upregulation of SOX2 as shown by enhanced resistance to radiation and metastatic potential in vitro. Interestingly, both the knockdown and overexpression of SOX2 led to increase in CD44+ population and induction of CSC properties in colorectal cancer following irradiation. Furthermore, selective genetic and pharmacological inhibition of the PI3K/AKT pathway, but not the MAPK pathway, attenuated SOX2-dependent CD44 expression and metastatic potential upon irradiation in vitro. Our findings suggested that SOX2 regulated by radiation-induced activation of PI3K/AKT pathway contributes to the induction of colorectal CSCs, thereby highlighting its potential as a therapeutic target.


Assuntos
Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Radiação , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais , Regulação para Cima , Linhagem Celular Tumoral , Movimento Celular/efeitos da radiação , Humanos , Receptores de Hialuronatos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Invasividade Neoplásica , Células-Tronco Neoplásicas/efeitos da radiação , Tolerância a Radiação/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Regulação para Cima/efeitos da radiação
14.
Free Radic Biol Med ; 164: 76-84, 2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33387605

RESUMO

Neutrophils are key cells from the innate immune system that destroy invading bacteria or viruses, thanks mainly to the non-mitochondrial reactive oxygen species (ROS) generated by the enzyme NADPH oxidase. Our aim was to study the response of neutrophils to situations of oxidative stress with emphasis on the impact on the NADPH oxidase complex. To mimic oxidative stress, we used gamma irradiation that generated ROS (OH•, O2•- and H2O2) in a quantitative controlled manner. We showed that, although irradiation induces shorter half-lives of neutrophil (reduced by at least a factor of 2), it triggers a pre-activation of surviving neutrophils. This is detectable by the production of a small but significant amount of superoxide anions, proportional to the dose (about 3 times that of sham). Investigations at the molecular level showed that this ROS increase was generated by the NADPH oxidase enzyme after neutrophils irradiation. The NADPH oxidase complex undergoes an incomplete assembly which includes p47phox and p67phox but excludes the G-protein Rac. Importantly, this irradiation-induced pre-activation is capable of considerably improving neutrophil reactivity. Indeed, we have observed that this leads to an increase in the production of ROS and the capacity of phagocytosis, leading to the conclusion that radiation induced ROS clearly behave as neutrophil primers.


Assuntos
NADPH Oxidases , Neutrófilos , Radiação , Espécies Reativas de Oxigênio , Humanos , Peróxido de Hidrogênio , NADPH Oxidases/genética , Fosfoproteínas , Superóxidos
15.
FEMS Microbiol Lett ; 368(1)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33469646

RESUMO

Evolution of multi-drug resistant bacteria has led to worldwide research to better understand the various resistance mechanisms in these strains. Every year, novel information on carbapenem resistance and its mechanisms is being discovered. In this study, radiation-mediated mutagenesis was used to transform a carbapenem-resistant Klebsiella pneumoniae strain to a carbapenem-susceptible bacterium. Through this process, we proved three conditions of loss of the OmpK35 and the OmpK36 genes and acquisition of blaCMY-10 worked together to produce carbapenem resistance in K. pneumoniae. Loss of only one of the porins did not evoke carbapenem resistance. This is the first report on the essential contribution of these three components of carbapenem resistance in K. pneumoniae.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Infecções por Klebsiella/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos da radiação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Mutagênese/efeitos da radiação , Porinas/genética , Porinas/metabolismo , Radiação , beta-Lactamases/genética , beta-Lactamases/metabolismo
16.
Arch Razi Inst ; 75(4): 439-449, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33403839

RESUMO

Tuberculin skin test, also known as the tuberculin or purified protein derivative (PPD) test, is an extensively applied diagnostic test for the detection of primary infection with Mycobacterium tuberculosis (Mtb). The production of PPD is accompanied by some difficulties that require a series of modifications in the production and purification processes. The present study aimed to determine the facilitation level of the manufacturing process by modifying evaluation methods for the production of PPD tuberculin. Mtb strains were cultured in Lowenstein-Jensen media, and the cultured strains were inoculated into the Dorset-Henley liquid medium by the biphasic medium of potato-Dorset-Henley. After incubation, flasks containing cultured strain were selected for bacterial inactivation, and the optimal gamma radiation dose(s) was determined. Tuberculoproteins were precipitated by ammonium sulfate (AS) and Trichloroacetic acid (TCA). Protein concentration was determined using the Bradford and Kjeldahl protein assay methods. Finally, the lymphocyte transformation test and potency test were performed. Based on the results, the Dorset-Henley liquid medium is suitable for the massive growth of the bacterium. The transferal of Mtb from solid to liquid medium was directly carried out without intermediate culture. It was found that during tuberculoprotein production, heating at 100&deg;C for 3 h would be safe for killing mycobacterium. Furthermore, the simultaneous use of heating and gamma irradiation (8 kGgy) killed all of the mycobacteria, while doses of 1, 1.5, and 7 kGy decreased a significant number of bacterial cells. The results also indicated that the concentration of tuberculoprotein extracted by TCA precipitation method was higher than that obtained by AS precipitation. The tuberculoproteins which were produced by these two methods in the lymphocyte transformation test were not significantly different in terms of potency (P&gt;0.05). Moreover, due to the high volume of produced protein, the protein measurement was more efficiently carried out by the Kjeldahl method, compared to the Bradford method. Finally, the results of the present study demonstrated that in addition to the novel approach of gamma irradiation, optimum methods are efficient and applicable in the production of PPD tuberculin.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Calefação/métodos , Mycobacterium tuberculosis/química , Radiação , Tuberculina/isolamento & purificação , Testes Diagnósticos de Rotina/instrumentação
17.
Am J Bot ; 108(1): 113-128, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33426651

RESUMO

PREMISE: Events of accelerated species diversification represent one of Earth's most celebrated evolutionary outcomes. Northern Andean high-elevation ecosystems, or páramos, host some plant lineages that have experienced the fastest diversification rates, likely triggered by ecological opportunities created by mountain uplifts, local climate shifts, and key trait innovations. However, the mechanisms behind rapid speciation into the new adaptive zone provided by these opportunities have long remained unclear. METHODS: We address this issue by studying the Venezuelan clade of Espeletia, a species-rich group of páramo-endemics showing a dazzling ecological and morphological diversity. We performed several comparative analyses to study both lineage and trait diversification, using an updated molecular phylogeny of this plant group. RESULTS: We showed that sets of either vegetative or reproductive traits have conjointly diversified in Espeletia along different vegetation belts, leading to adaptive syndromes. Diversification in vegetative traits occurred earlier than in reproductive ones. The rate of species and morphological diversification showed a tendency to slow down over time, probably due to diversity dependence. We also found that closely related species exhibit significantly more overlap in their geographic distributions than distantly related taxa, suggesting that most events of ecological divergence occurred at close geographic proximity within páramos. CONCLUSIONS: These results provide compelling support for a scenario of small-scale ecological divergence along multiple ecological niche dimensions, possibly driven by competitive interactions between species, and acting sequentially over time in a leapfrog pattern.


Assuntos
Asteraceae , Radiação , Evolução Biológica , Ecossistema , Especiação Genética , Filogenia
18.
Arq Bras Oftalmol ; 84(1): 87-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33470348

RESUMO

This is a rare case report of acute, paracentral corneal melting and perforation occurring 1 week after an uneventful cataract surgery, with discussions on possible pathogenetic mechanisms. Relevant literature was also reviewed. Herein, a case of an 86-year-old woman with acute, paracentral, and sterile corneal melting and perforation in her left eye at 1 week after an uncomplicated cataract extraction is described. This occurs at the base of ocular surface disorders due to previous radiation of her lower eyelid and cheeks for the treatment of cancer and previously undiagnosed rheumatoid arthritis. She underwent surgical treatment using Gundersen's conjunctival flap for the existing perforation due to low visual expectancies and reluctance to undergo corneal keratoplasty due to the risk of corneal graft rejection. The risk of coming across an acute corneal melting after an uncomplicated cataract surgery in the eyes with ocular surface disorders should always be considered.


Assuntos
Artrite Reumatoide , Extração de Catarata , Catarata , Doenças da Córnea , Radiação , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Doenças da Córnea/etiologia , Doenças da Córnea/cirurgia , Feminino , Humanos
19.
Ecotoxicol Environ Saf ; 208: 111579, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396102

RESUMO

Studies about radiation damage in vivo are very significant for healthy risk assessment as well as cancer radiotherapy. Ceramide as a second messenger has been found to be related to radiation-induced apoptosis. However, the detailed mechanisms in living systems are still not fully understood. In the present study, the effects of ceramide in gamma radiation-induced response were investigated using Caenorhabditis elegans. Our results indicated that ceramide was required for gamma radiation-induced whole-body germ cell apoptosis by the production of radical oxygen species and decrease of mitochondrial transmembrane potential. Using genetic ceramide synthase-related mutated strains and exogenous C16-ceramide, we illustrated that ceramide could regulate DNA damage response (DDR) pathway to mediate radiation-induced germ cell apoptosis. Moreover, ceramide was found to function epistatic to pmk-1 and mpk-1 in MAPK pathway to promote radiation-induced apoptosis in Caenorhabditis elegans. These results demonstrated ceramide could potentially mediated gamma radiation-induced apoptosis through regulating mitochondrial function, DDR pathway and MAPK pathway.


Assuntos
Caenorhabditis elegans/fisiologia , Ceramidas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos da radiação , Proteínas de Caenorhabditis elegans/genética , Ceramidas/metabolismo , Dano ao DNA , Células Germinativas/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Radiação , Espécies Reativas de Oxigênio/metabolismo
20.
Crit Rev Oncol Hematol ; 159: 103229, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33482343

RESUMO

AIMS: The limbic circuit (LC) is devoted to linking emotion to behavior and cognition. The injury this system results in post-RT cognitive dysfunction. The aim of this study is to create the first radiation oncologist's practical MR-based contouring guide for the delineation of the LC for the everyday clinical practice and education. METHODS: An anonymized diagnostic 3.0 T T1-weighted BRAVO MRI sequence from a healthy patient with typical brain anatomy was used to delineate LC. For each structure key anatomical contours were completed by radiation oncologists, along with a neuro-radiologist to generate the final version of the LC atlas. RESULTS: a step-by-step MR-based atlas of LC was created. Key structures of the LC, such as, cingulate gyrus, fornix, septal region, mammillary bodies, thalamus and the hippocampal-amygdala formation were contoured. CONCLUSIONS: This article provides the recommendations for the first contouring atlas of LC in the setting of patients receiving RT and education.


Assuntos
Órgãos em Risco , Radiação , Humanos , Sistema Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Planejamento da Radioterapia Assistida por Computador
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