Abstract Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Abstract Pesticides, as Temephos and Roundup, and surfactants, like Sodium Dodecyl Sulfate (SDS), when discharged into the environment, are harmful to non-target wildlife, especially fish. To evaluate the effects of those chemicals alone and their binary combinations, we assessed the histological alterations in Danio rerio gills after 15 days of exposure to Temephos (1ppm), Roundup (10ppm), SDS (2ppm), SDS plus Temephos (2ppm+1ppm), SDS plus Roundup (2ppm+10ppm) and Temephos plus Roundup (1ppm+10ppm). Hyperplasia, a regressive change, was significant in all exposed groups. The progressive change, complete fusion of lamellae, was significantly intensive in Roundup plus Temephos group. Regarding circulatory disturbances, vascular congestion was significant intensive in SDS group, while severe aneurysm was observed in Roundup group. Although xenobiotics in the blend are biologically complex, mainly for long periods, combinatorial exposure incremented only complete fusion of lamellae. Our results reinforce the rationalization of indiscriminate use of those compounds alone or in combination.

Abstract Herein we evaluated the histopathological alterations and expression patterns of multixenobiotic resistence (MXR) and autophagic proteins in liver samples of fish chronically exposed to anthropogenic contaminants in a highly polluted river, and then again after they had been transferred to good quality water. Two groups were established: euthanized on the day of capture (0 h), and maintained for 30 days in a tank (30 d). The fish of 0 h presented liver with vacuolated and hypertrophic hepatocytes. Also, it was observed strong immunostaining of cathepsin-D, LC3-II and P-gp. Necrosis and apoptosis were also observed throughout the liver. Conversely, the second group (30 d) showed recovery of the liver normal histology and weak immunoreaction of the studied proteins. So, our results indicated that there was a hepatic recovery in the fish kept in good quality water, as showed by the decreased expression of cathepsin-D, LC3-II, and the MXR (P-gp). Therefore, the alterations here observed could be proposed as potential biomarkers to be tested for following the impacts of remediation or mitigation measures to environmental impacts.

ABSTRACT It is widely known that high fat diet (HFD) can contribute to the advent of health problems. Recent studies have indicated that obesity imposes a hemodynamic overload to the kidneys. In order to further investigate such injuries, two groups of six Swiss mice each were fed with a controlled AIN93G diet or a high fat (AIN93G modified) diet for eight weeks. Blood samples were collected to determine the hormonal, lipid profile, glucose, urea, and creatinine levels. Histopathological and immunohistochemical analysis were carried out to analysis the kidney damage. Fractions of renal membranes were prepared to assess the Na,K-ATPase activity, lipid peroxidation, total cholesterol, and phospholipid content. The results indicated that the blood lipid profile, urea and creatinine was not altered by the HFD. On the other hand, it was observed in HFD diet mice elevated glucose blood levels along with an augment on insulin and a decrease on corticosterone release. HFD provoked a reduction in the diameter of the convoluted tubules and cell volume in Bowman’s capsule and an increased number of positive cells with Na,K-ATPase, but reduced the Na,K-ATPase activity and the cholesterol content in the kidney cell membrane but favored the lipid peroxidation.

Abstract A novel lectin was isolated from the seeds of Chenopodium quinoa. To achieve this end, the crude extract from the quinoa was submitted to two purification steps, Sephadex G50 and Mono Q. The hemagglutinating activity showed that this lectin agglutinates human erythrocytes. Its activity is inhibited by glucose and mannose, and remained stable under a wide range of pH levels and temperatures. The quinoa lectin was found to be a heterodimeric lectin of approximately 60 kDa, consisting of two subunits of approximately 25 kDa and 35 kDa. This lectin had its antimicrobial activity tested against several bacteria strains and effectively inhibited three strains. These strains were all Gram-negative, making this lectin a promising antimicrobial tool.

INTRODUÇÃO: O uso de suplementos ergogênicos farmacológicos e nutricionais cresce a cada dia no ambiente esportivo. A creatina e os esteroides anabólicos são os recursos ergogênicos mais procurados ultimamente. OBJETIVO: Avaliar as alterações histológicas e morfométricas do músculo sóleo de ratos que receberam suplementos e foram submetidos a treinamento físico (TF) de natação. MÉTODOS: Foram utilizados 50 ratos, distribuidos em cinco grupos: três não submetidos à atividade física (controles) e dois que receberam treinamento de natação (treinados). Um grupo controle recebeu apenas ração (grupo controle ração), dois grupos (um controle e outro treinado) receberam diariamente 3,3 mg de creatina por grama de dieta dissolvida em água aplicada oralmente via gavagem, e os outros dois grupos (um controle e outro treinado) receberam injeção intramuscular do esteroide anabolizante decanoato de nandrolona (Deca-durabolin(r) - Organon) 5 mg/kg duas vezes por semana. Os grupos treinados foram submetidos ao TF com duração de 60 min/sessão de segunda a sexta-feira por nove semanas, e foram sacrificados no final deste período. Após o sacrifício, o músculo sóleo foi retirado, fixado em formalina (10%) tamponada e incluído em parafina. Os cortes histológicos foram corados pela técnica de hematoxilina-eosina para avaliação de hiperplasia e hipertrofia muscular. Para análise dos dados aplicou-se a análise de variância ANOVA One-Way com post hoc de Tukey-Kramer com nível de significância de 5%. RESULTADOS: Foi demonstrado que a creatina associada ao exercício provavelmente aumente o espaço intersticial no músculo esquelético sem alterar o tamanho ou número de fibras musculares, enquanto que o anabolizante aumentou o número de fibras musculares por área de músculo analisada, embora nenhuma alteração tenha sido observada na área da fibra. CONCLUSÃO: O músculo de ratos submetidos ao treinamento de natação responde diferentemente frente ao tipo de recurso ergogênico utilizado.

INTRODUCTION: The use of pharmacologic and nutritional ergogenic supplements is growing every day in sports environment. Creatine and anabolic steroids are the most popular ergogenic resources used lately. OBJECTIVE: To evaluate the histological and morphometric changes of the soleus muscle of rats receiving supplements and submitted to physical training (swimming). METHODS: 50 rats were allocated into five groups: three did not undergo physical activity (controls) and two that received swimming training (trained). A control group received only rat chow (control chow group), two groups (one control and one trained) received 3.3mg of creatine per gram of diet dissolved in water daily applied orally via gavage, and the other two groups (control and other trained) received intramuscular injections of the anabolic steroid nandrolone decanoate (Deca-durabolin(r) - Organon) 5mg/kg twice weekly. The trained groups were submitted to the physical training 60min/day lasting from Monday to Friday for 9 weeks and were sacrificed at the end of the period. After sacrifice, the soleus muscle was removed, fixed in buffered formalin (10%) and embedded in paraffin. The histological sections were stained by hematoxylin-eosin for evaluation of muscle hyperplasia and hypertrophy. For data analysis we applied the One-Way ANOVA with post hoc Tukey-Kramer significance level of 5%. RESULTS: It was shown that creatine during exercise probably increase the interstitial space in skeletal muscle without changing the size or number of muscle fibers, whereas the anabolic agent increased the number of muscle fibers per muscle area examined, though no changes have been observed in the area of the fiber. CONCLUSION: The muscle of rats submitted to swimming training responds differently opposite type of ergogenic aid used.

INTRODUCCIÓN: El uso de suplementos ergogénicos farmacológicos y nutricionales crece, cada día, en el ambiente deportivo. La creatina y los esteroides anabólicos son los recursos ergogénicos más procurados en los últimos tiempos. OBJETIVO: Evaluar las alteraciones histológicas y morfométricas del músculo sóleo de ratones que recibieron suplementos y fueron sometidos a entrenamiento físico (EF) de natación. MÉTODOS: Se utilizaron 50 ratones, distribuidos en cinco grupos: tres de estos no sometidos a la actividad física (controles) y dos que recibieron entrenamiento de natación (entrenados). Un grupo de control recibió solamente ración (grupo de controle por ración), dos grupos (uno de control y otro entrenado) recibieron diariamente 3,3 mg de creatina, por gramo de dieta, disuelta en agua aplicada oralmente vía gavaje, y los otros dos grupos (uno de control y otro entrenado) recibieron inyección intramuscular del esteroide anabolizante decanoato de nandrolona (Deca-durabolin(r) - Organon), 5 mg/kg dos veces por semana. Los grupos entrenados fueron sometidos al EF, con duración de 60 min/sesión, de lunes a viernes durante nueve semanas, y fueron sacrificados al final de este período. Después del sacrificio, el músculo sóleo fue retirado, fijado en formalina (10%) tamponada e insertado en parafina. Los cortes histológicos fueron coloridos mediante la técnica de hematoxilina-eosina para evaluación de hiperplasia e hipertrofia muscular. Para el análisis de los datos se aplicó el análisis de variancia ANOVA One-Way con post hoc de Tukey-Kramer, con nivel de significancia de 5%. RESULTADOS: Se demostró que la creatina, vinculada al ejercicio, aumenta probablemente el espacio intersticial en el músculo esquelético, sin alterar el tamaño ni el número de fibras musculares, mientras que el anabolizante aumentó la cantidad de fibras musculares por área de músculo que se analizó, aunque no se observó cualquier alteración en el área de la fibra. CONCLUSIÓN: El músculo de ratones, sometidos al entrenamiento de natación, responde de manera diferente frente al tipo de recurso ergogénico utilizado.

Baccharis trimera (Less.) (Asteraceae), popularmente conhecida como "carqueja", é uma espécie comumente empregada na medicina tradicional no tratamento ou prevenção de doenças. Nesse contexto, o objetivo deste trabalho foi estudar a atividade antibacteriana do extrato bruto hidroalcoólico de B. trimera frente às bactérias Gram-positivas (Staphylococcus aureus ATCC 29213, Staphylococcus saprophyticus ATCC 15305, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 19433) e bactérias Gram-negativas (Escherichia coli EHEC ATCC 43895, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 27736 e Salmonella typhi ATCC 19430) de interesse clínico. A susceptibilidade antibacteriana foi avaliada pelo método de microdiluição em caldo conforme estabelecido pelo CLSI (antigo NCCLS). O extrato de B. trimera mostrou atividade contra bactérias Gram-positivas, sendo o resultado mais interessante o obtido por S. epidermidis, que apresentou Concentração Inibitória Mínima de 250 μg/mL. Esses resultados indicam que B. trimera possui potencial atividade bacteriostática contra bactérias Gram-positivas de interesse médico e podem apresentar subsídios para estudos posteriores do uso de compostos isolados dessa espécie como futuros agentes antimicrobianos.

Baccharis trimera (Less.) (Asteraceae), popularly know as "carqueja", is a species commonly used in folk medicine for the treatment or prevention of diseases. In this context, the purpose of this work was to study the antibacterial activity of crude hydroalcoholic extract from Baccharis trimera against Gram-positive bacterial strains (Staphylococcus aureus ATCC 29213, Staphylococcus saprophyticus ATCC 15305, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 19433) and Gram-negative bacteria (Escherichia coli EHEC ATCC 43895, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 27736, Salmonella typhi ATCC 19430) of clinical interest. Antibacterial susceptibility was evaluated by broth microdilution assay following the CLSI (formerly the NCCLS) guidelines. The extract from B. trimera showed antibacterial activity against Gram-positive bacteria and the most interesting result was obtained against S. epidermidis that presented Minimal Inhibitory Concentration of 250μg/mL. These results indicate that B. trimera have bacterisostatic potential against Gram-positive bacterial strains of medical interest and could serve as a base for further studies on the use of isolated compounds from this species as future antimicrobials.

INTRODUÇÃO: Aproximadamente 80% das neoplasias malignas de pele não-melanomas são carcinomas basocelulares (CBC). Apesar das raras metástases, esses tumores são localmente agressivos. As metaloproteinases de matriz (MMPs), especialmente as MMP-2 e 9, são importantes no processo de invasão. Em contrapartida, os inibidores teciduais das MMPs (TIMPs) têm como principal função a inibição dessas enzimas. OBJETIVO: Investigar a associação de variáveis clinicopatológicas de pacientes portadores de CBC com a expressão de MMP-2, MMP-9, TIMP-1 e TIMP-2. MATERIAL E MÉTODOS: Foram selecionados 31 casos de CBC, sendo então obtidos, retrospectivamente, os dados referentes a idade, sexo e tamanho da lesão. Cortes histológicos das lesões foram submetidos a reação imuno-histoquímica pela técnica estreptavidina-biotina-peroxidase para detecção dos antígenos de interesse. Índices de imunomarcação foram construídos e comparados com os dados previamente obtidos. RESULTADOS: Observou-se correlação significativa entre idade e tamanho da lesão (R = 0,532; p = 0,008). Não foram observadas correlações significativas entre as outras variáveis e a expressão imuno-histoquímica dos antígenos de interesse. CONCLUSÃO: A expressão das metaloproteinases e de seus inibidores teciduais não parece ser influenciada pelos parâmetros investigados. Estudos adicionais são necessários para melhor compreensão de sua associação com o comportamento biológico do CBC.

INTRODUCTION: Approximately 80% of non-melanoma skin neoplasias are basal cell carcinomas (BCC). Although metastasis is rare, BBC carcinomas are locally aggressive tumors. Matrix metalloproteinases (MMPs), mainly MMP-2 and MMP-9, play an important role on the invasion process. On the other hand, tissue inhibitors of MMPs (TIMPs) have the main function of inhibiting these enzymes. OBJECTIVE: To investigate the association of clinical-pathological variables of BCC patients with the expression of MMP-2 and MMP-9, TIMP-1 and TIMP-2. Methods: Thirty-one BCC cases were selected. Gender, age of the patients and size of the lesions were obtained retrospectively. Histological cuts of the lesions were exposed to immunohistochemistry reaction by use of the streptavidine-biotin peroxidase technique in order to detect antigens. Immunomarking parameters were established and compared with previous data. RESULTS: A significant correlation between age and size of the lesion was observed (R = 0.532; p = 0.008). No significant correlations between other variables and immunohistochemical expression of antigens were observed. CONCLUSION: The expression of MMPs and TIMPs does not seem to be influenced by the parameters investigated in this work. Additional studies should be made to better understand its association with the biological behavior of basal cell carcinomas.