Noninvasive Red Laser Intervention before Radiotherapy of Triple-negative Breast Cancer in a Murine Model.

Radiotherapy is a well-established cancer treatment; it is estimated that approximately 52% of oncology patients will require this treatment modality at least once. However, some tumors, such as triple-negative breast cancer (TNBC), may present as radioresistant and thus require high doses of ionizing radiation and a prolonged period of treatment, which may result in more severe side effects. Moreover, such tumors show a high incidence of metastases and decreased survival expectancy of the patient. Thus, new strategies for radiosensitizing TNBC are urgently needed. Red light therapy, photobiomodulation, has been used in clinical practice to mitigate the adverse side effects usually associated with radiotherapy. However, no studies have explored its use as a radiosensitizer of TNBC. Here, we used TNBC-bearing mice as a radioresistant cancer model. Red light treatment was applied in three different protocols before a high dose of radiation (60 Gy split in 4 fractions) was administered. We evaluated tumor growth, mouse clinical signs, total blood cell counts, lung metastasis, survival, and levels of glutathione in the blood. Our data showed that the highest laser dose in combination with radiation arrested tumor progression, likely due to inhibition of GSH synthesis. In addition, red light treatment before each fraction of radiation, regardless of the light dose, improved the health status of the animals, prevented anemia, reduced metastases, and improved survival. Collectively, these results indicate that red light treatment in combination with radiation could prove useful in the treatment of TNBC.

Noninvasive Red Laser Intervention before Radiotherapy of Triple-negative Breast Cancer in a Murine Model.

Radiotherapy is a well-established cancer treatment; it is estimated that approximately 52% of oncology patients will require this treatment modality at least once. However, some tumors, such as triple-negative breast cancer (TNBC), may present as radioresistant and thus require high doses of ionizing radiation and a prolonged period of treatment, which may result in more severe side effects. Moreover, such tumors show a high incidence of metastases and decreased survival expectancy of the patient. Thus, new strategies for radiosensitizing TNBC are urgently needed. Red light therapy, photobiomodulation, has been used in clinical practice to mitigate the adverse side effects usually associated with radiotherapy. However, no studies have explored its use as a radiosensitizer of TNBC. Here, we used TNBC-bearing mice as a radioresistant cancer model. Red light treatment was applied in three different protocols before a high dose of radiation (60 Gy split in 4 fractions) was administered. We evaluated tumor growth, mouse clinical signs, total blood cell counts, lung metastasis, survival, and levels of glutathione in the blood. Our data showed that the highest laser dose in combination with radiation arrested tumor progression, likely due to inhibition of GSH synthesis. In addition, red light treatment before each fraction of radiation, regardless of the light dose, improved the health status of the animals, prevented anemia, reduced metastases, and improved survival. Collectively, these results indicate that red light treatment in combination with radiation could prove useful in the treatment of TNBC.

New Insights in Phenothiazinium-Mediated Photodynamic Inactivation of Candida Auris.

In recent years, Candida auris has emerged as a hazardous hospital-acquired pathogen. Its resistance to antifungal treatments makes it challenging, requiring new approaches to manage it effectively. Herein, we aimed to assess the impact of photodynamic inactivation mediated by methylene blue (MB-PDI) or 1,9-dimethyl MB (DMMB-PDI) combined with a red LED against C. auris. To evaluate the photoinactivation of yeasts, we quantified colony-forming units and monitored ROS production. To gain some insights into the differences between MB and DMMB, we assessed lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm). After, we verified the effectiveness of DMMB against biofilms by measuring metabolic activity and biomass, and the structures were analyzed through scanning electron microscopy and optical coherence tomography. We also evaluated the cytotoxicity in mammalian cells. DMMB-PDI successfully eradicated C. auris yeasts at 3 µM regardless of the light dose. In contrast, MB (100 µM) killed cells only when exposed to the highest dose of light. DMMB-PDI promoted higher ROS, LPO and ΔΨm levels than those of MB. Furthermore, DMMB-PDI was able to inhibit biofilm formation and destroy mature biofilms, with no observed toxicity in fibroblasts. We conclude that DMMB-PDI holds great potential to combat the global threat posed by C. auris.

Ethylene vinyl acetate copolymer is an efficient and alternative passive sampler of hydrophobic organic contaminants. A comparison with silicone rubber.

There is a growing demand for assessing the concentrations of Hydrophobic Organic Contaminants (HOCs) in aquatic environments, including Persistent Organic Pollutants (POPs). The hydrophobicity of POPs challenges their quantification in waters due to the sub-trace concentrations, especially when using conventional spot sampling. The results from the conventional samples are only a "snapshot" of the concentrations (if detected) at the specific sampling moment. Contrary, passive sampling provides average concentration levels over weeks or months from the quantification of accumulated pollutants during the deployment period. The present work compared ethylene vinyl acetate (EVA) and silicon rubber (SR) as monophasic passive samplers to measure dissolved concentrations of HOCs. Four classes of POPs were studied: (i) polychlorinated dibenzo-p-dioxins (PCDDs), (ii) polychlorinated dibenzofurans (PCDFs), (iii) polychlorinated biphenyls (PCBs), including the dioxin-like congeners, and (iv) the polybrominated diphenyl ethers (PBDEs). The polymer-water partition coefficients (Kpw), determined by the cosolvent and crossed calibrations, were, on average, one logarithmic unit larger in EVA than in the SR. The diffusion coefficients (Dp) estimated by the "film-stacking" method were, on average, two orders of magnitude smaller in the EVA than in the SR. For both polymers, the theoretical model of mass transfer resistance confirmed that the water boundary layer controlled the absorption, thus allowing the use of Performance Reference Compounds (PRCs) to estimate the in-situ sampling rates. Larger Kpw's in EVA may be an advantage because they imply longer time scales to reach equilibrium, higher absorption capacities and hence a higher absorbed contaminant mass, especially for compounds that reach equilibrium relatively faster (log Kow < 5). In addition, the longer times to attain equilibrium for EVA maintain this sampler longer in the linear phase of absorption, and the time-weighted average concentration may only be assessed in this phase when the compounds have not yet reached equilibrium.

Monitoring tar spot disease in corn at different canopy and temporal levels using aerial multispectral imaging and machine learning.

Introduction: Tar spot is a high-profile disease, causing various degrees of yield losses on corn (Zea mays L.) in several countries throughout the Americas. Disease symptoms usually appear at the lower canopy in corn fields with a history of tar spot infection, making it difficult to monitor the disease with unmanned aircraft systems (UAS) because of occlusion. Methods: UAS-based multispectral imaging and machine learning were used to monitor tar spot at different canopy and temporal levels and extract epidemiological parameters from multiple treatments. Disease severity was assessed visually at three canopy levels within micro-plots, while aerial images were gathered by UASs equipped with multispectral cameras. Both disease severity and multispectral images were collected from five to eleven time points each year for two years. Image-based features, such as single-band reflectance, vegetation indices (VIs), and their statistics, were extracted from ortho-mosaic images and used as inputs for machine learning to develop disease quantification models. Results and discussion: The developed models showed encouraging performance in estimating disease severity at different canopy levels in both years (coefficient of determination up to 0.93 and Lin's concordance correlation coefficient up to 0.97). Epidemiological parameters, including initial disease severity or y0 and area under the disease progress curve, were modeled using data derived from multispectral imaging. In addition, results illustrated that digital phenotyping technologies could be used to monitor the onset of tar spot when disease severity is relatively low (< 1%) and evaluate the efficacy of disease management tactics under micro-plot conditions. Further studies are required to apply and validate our methods to large corn fields.

Safety and Clinical Impact of a Single Red Light Irradiation on Breast Tumor-Bearing Mice.

Low-level light therapy has been used in health care as a therapeutic strategy for different diseases. However, its effects on cancer are controversial. This work evaluated the effects of three energies on breast cancer-bearing mice after a single red light-emitting diode (LED) irradiation. 4T1 cells were inoculated into the mammary fat pad of female BALB/c mice. When tumor volume reached 100 mm3 , animals were irradiated by a LED irradiator (660 ± 11 nm) with energies of 1.2, 3.6, and 6.0 J. Control without irradiation and healthy animals were also evaluated. Mice were monitored regarding tumor volume and total blood count. After euthanasia, their organs were examined. We observed that a single irradiation does not increase tumor volume. All irradiated groups exhibited better clinical conditions than control, which presented a significant decrease in platelet and red blood cell levels compared with healthy mice. The energy of 3.6 J arrested neutrophil-lymphocyte rate besides promoting longer survival and a lower number of metastatic nodules in the lungs. These findings suggest that a single red LED irradiation causes no impact on the course of the disease. Besides, the intermediary dose-effect should be further investigated since it seems to promote better outcomes on breast cancer-bearing mice.

Inhibition kinetics of digestive proteases for Anticarsia gemmatalis.

Anticarsia gemmatalis Hübner, 1818 (Lepidoptera) is a major pest of soybean in the Brazil. It is known that the reduction of proteolytic activity by the ingestion of protease inhibitors reduces digestion and larval development of the insects. Control via inhibition of the digestive enzymes necessitates deeper knowledge of the enzyme kinetics and the characterization of the inhibition kinetics of these proteases, for better understanding of the active centers and action mechanisms of this enzyme. Trypsin-like proteases found in the gut of Anticarsia gemmatalis were purified in a p-aminobenzamidine agarose column. Kinetic characterization showed KM 0.503 mM for the L-BApNA substrate; Vmax= 46.650 nM s-1; Vmax/[E]= 9.256 nM s-1 mg L-1 and Vmax/[E]/KM= 18.402 nM s-1 mg L-1 mM. The Ki values for the inhibitors benzamidine, berenil, SKTI and SBBI were 11.2 µM, 32.4 µM, 0.25 nM and 1.4 nM, respectively, and all revealed linear competitive inhibition. The SKTI showed the greatest inhibition, which makes it a promising subject for future research to manufacture peptide mimetic inhibitors.

Evaluation of HLA-G immune checkpoint molecule in melanocytic lesions / Avaliação da molécula de checkpoint imunológico HLA-G em lesões melanocíticas

ABSTRACT The human leukocyte antigen-G (HLA-G) is a non-classical molecule of the major histocompatibility complex. HLA-G has been associated with the process of tumorigenesis and tumor escape. In this study, we aim to evaluate the HLA-G expression in melanocytic lesions and in melanoma for determining when melanocytic lesions start its expression. Twenty-two skin biopsies samples were submitted to immunohistochemistry; HLA-G expression was detected in 63.6% of the samples. This expression in melanocytic cells was significantly higher in melanoma than in benign melanocytic lesions (p < 0.002). Our results suggest that HLA-G expression starts late in the process of tumorigenesis.

RESUMEN El antígeno leucocitario humano G (HLA-G) es una molécula no clásica del complejo principal de histocompatibilidad que ha sido asociada al proceso de tumorigénesis y escape tumoral. En este estudio, nuestro objetivo es evaluar la expresión de HLA-G en lesiones melanocíticas y en el melanoma para determinar cuando las lesiones melanocíticas comienzan su expresión. Veintidós muestras de biopsias de piel se estudiaron mediante inmunohistoquímica; se detectó la expresión de HLA-G en el 63,6% de las muestras. Esa expresión en las células melanocíticas fue significativamente mayor en el melanoma que en lesiones melanocíticas benignas (p < 0,002). Nuestros resultados sugieren que la expresión de HLA-G empieza tardíamente en el proceso de tumorigénesis.

RESUMO O antígeno leucocitário humano G (HLA-G) é uma molécula não clássica do complexo principal de histocompatibilidade que tem sido associada ao processo de tumorigênese e escape tumoral. Neste estudo, objetivamos avaliar a expressão de HLA-G em lesões melanocíticas e no melanoma para determinar quando as lesões melanocíticas iniciam sua expressão. Vinte e duas amostras de biópsias de pele foram submetidas à imuno-histoquímica; a expressão de HLA-G foi observada em 63,6% das amostras. Essa expressão nas células melanocíticas foi significativamente maior no melanoma do que em lesões melanocíticas benignas (p < 0,002). Nossos resultados sugerem que a expressão de HLA-G se inicia tardiamente no processo da tumorigênese.

Does mechanical damage on soybean induces the production of flavonoids?

The response of plants to grazing includes the production of chemical defense compounds such as proteases inhibitors and secondary metabolites as flavonoids, which makes them less palatable to feeding and negatively affecting the physiology of insects. The aim of this study was to evaluate the phytochemical response of soybean cultivars (Glycine max (L.) Merrill) resistant (IAC-17, IAC-24) and susceptible (IAC-P1) to insects after mechanical damage. These cultivars were mechanically injured, and after 24 hours samples of these plants were analyzed by HPLC to identify and quantify flavonoids. The flavonoids daidzein, quercetin, and rutin were quantified, with the highest concentration of daidzin in soybean cultivars after mechanical damage. Rutin was biosynthesized by IAC-24. The cultivars IAC-PL1, IAC-17, and IAC-24 did not show a flavonoid response to mechanical damage. The soybean cultivars are not dependent on mechanical damage to produce flavonoids.

Protease inhibitory, insecticidal and deterrent effects of the trypsin-inhibitor benzamidine on the velvetbean caterpillar in soybean.

The recognition of protease inhibitors with insecticidal activity is important as a basis for the development of mimetic peptides with potential use as biorational insecticides. We sprayed benzamidine on soybean plants and assessed whether this potent synthetic trypsin-inhibitor has protease inhibitory, insecticidal and deterrent effects on the velvetbean caterpillar Anticarsia gemmatalis Hübner (Lepidoptera: Erebidae). Activity of trypsin inhibition in soybean leaves was increased and total proteolytic activity in the midgut extract from larvae fed on these leaves was reduced by benzamidine. Different concentrations of benzamidine sprayed on the plant caused approximately 50 % of larval mortality, and larval choice and moth preference and oviposition were all negatively affected. Low concentrations of benzamidine increased mortality and hindered insect choice and oviposition as well as higher doses. Since many synthetic protease inhibitors are usually expensive, small doses of benzamidine may be effective to protect soybean against A. gemmatalis attack. Our results highlight the potential of synthetic protease inhibitors for insecticidal and deterrent purposes in insect pest management.

Biochemical responses of Anticarsia gemmatalis (Lepidoptera: Noctuidae) in soybean cultivars sprayed with the protease inhibitor berenil.

The damage caused by Anticarsia gemmatalis motivates this study on the adaptive mechanisms of the insect to soybean. The lipoxygenase pathway produces and releases jasmonic acid, involved in the regulation of the plant defense genes, which encodes protease inhibitor (PI) production. Three soybean cultivars IAC-18, IAC-24, and Foscarin-31 were sprayed with water and berenil, a synthetic inhibitor, at 0.60 and 1.0% (w/v) and then infested with A. gemmatalis larvae. The lipoxygenase (LOX) activity increased in the leaves of Foscarin-31, IAC-18, and IAC-24 by 87, 81, and 78%, respectively, after 24 h of A. gemmatalis damage. IAC-18 revealed the lowest increase in PI when compared to the other cultivars. Protease, amidase, and esterase activities in soybean larvae dropped drastically after berenil application. PIs may be included in the control strategies of A. gemmatalis in soybean by lowering the digestive enzyme activity in the larval midgut, thus affecting insect growth and development.

O lúdico no processo pedagógico da educação infantil: importante, porém ausente / The playful in the pedagogic process of infantile education: important but absent / El lúdico en el process pedagógico de la educación infantil: importante pero ausente

Este estudo observou e analisou a presença do lúdico no fazer educacional das professoras das escolas infantis das redes pública e particular da cidade de São José do Rio Preto. Por meio de pesquisas bibliográfica e empírica, foram abordadas escolas distribuídas nos quatro setores da cidade, nas quais se realizou, primeiramente, uma observação sistematizada e posteriormente a aplicação de um questionário junto às professoras. O principal objetivo foi verificar se no cotidiano escolar das unidades de ensino infantil envolvidas na pesquisa havia ou não situações de utilização de atividades lúdicas, planejamento das atividades ou seu uso aleatório, assim como a compreensão das professoras acerca do brincar na educação infantil. Os dados coletados foram tratados de modo comparativo entre os dois modelos de escolas compreendidas nos setores público e privado, o que possibilitou traçar um percurso do lúdico na educação infantil e no fazer pedagógico das professoras que, na época, atuavam nos distintos segmentos com a respectiva faixa etária

This study observed and analyzed the presence of playful teaching practice on the educational action of teachers in the kindergarten school both from the public and private sectors in the city of São José do Rio Preto. By means of a bibliographical and empirical research, schools from four different parts of the city were evaluated and systematically observed. Later, a questionnaire was applied to the teachers. The main objective was to verify whether or not there were situations in which playful activities would be part of the teacher's daily agenda, either as a planned activity or even used randomly, as well as the understanding of the teachers concerning this matter in the infantile education

Este estudio analisó la presencia del juguete en el hacer pedagógico de las maestras en guarderías de la red pública de la ciudad de São José do Rio Preto. Por medio de encuestas bibliográficas y empíricas, fueran abordadas escuelas distribuidas en los cuatro sectores de la ciudad en los cuales se realizó una observación sistematizada, y después la aplicación de una encuesta con los maestros. El objectivo primero fue verificar si en el cotidiano de las escuelas tenía o no situaciones de utilización de actividades lúdicas, planeamento de las actividades o empleo obligatorio, como también la comprensión de las mismas acerca de los juguetes infantiles