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1.
Nitric Oxide ; 148: 1-12, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636582

RESUMO

Epidemiological studies show a strong correlation between diabetes and the increased risk of developing different cancers, including melanoma. In the present study, we investigated the impact of a streptozotocin (STZ)-induced hyperglycemic environment on B16F10-Nex2 murine melanoma development. Hyperglycemic male C57Bl/6 mice showed increased subcutaneous tumor development, partially inhibited by metformin. Tumors showed increased infiltrating macrophages, and augmented IL-10 and nitric oxide (NO) concentrations. In vivo neutralization of IL-10, NO synthase inhibition, and depletion of macrophages reduced tumor development. STZ-treated TLR4 KO animals showed delayed tumor development; the transfer of hyperglycemic C57Bl/6 macrophages to TLR4 KO reversed this effect. Increased concentrations of IL-10 present in tumor homogenates of hyperglycemic mice induced a higher number of pre-angiogenic structures in vitro, and B16F10-Nex2 cells incubated with different glucose concentrations in vitro produced increased levels of IL-10. In summary, our findings show that a hyperglycemic environment stimulates murine melanoma B16F10-Nex2 primary tumor growth, and this effect is dependent on tumor cell stimulation, increased numbers of macrophages, and augmented IL-10 and NO concentrations. These findings show the involvement of tumor cells and other components of the tumor microenvironment in the development of subcutaneous melanoma under hyperglycemic conditions, defining novel targets for melanoma control in diabetic patients.


Assuntos
Hiperglicemia , Interleucina-10 , Macrófagos , Melanoma Experimental , Camundongos Endogâmicos C57BL , Óxido Nítrico , Animais , Interleucina-10/metabolismo , Óxido Nítrico/metabolismo , Masculino , Hiperglicemia/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Linhagem Celular Tumoral
2.
Braz J Microbiol ; 54(4): 2551-2560, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37589929

RESUMO

Luiz Rodolpho Travassos, a Brazilian scientist recognized in several areas of research, began his studies in the field of oncology in the late 1970s when he took a sabbatical at the Memorial Sloan Kettering Cancer Center, NY, USA. At that time, the discovery and characterization of human melanoma glycoprotein antigens yielded important publications. This experience allowed 16 years later, and Dr. Travassos founded UNONEX, significantly contributing with discoveries in the area of oncology and training of researchers. This review will address all the contributions of team of researchers who, together with Dr. Travassos, collaborated with investigations into molecules and processes that lead to the development of melanoma.


Assuntos
Melanoma , Humanos , Brasil , Biologia
3.
Cad Saude Publica ; 39(7): e00223122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37585904

RESUMO

This study sought to synthesize and reinterpret findings from primary qualitative studies on the experience of health professionals in caring for people with anorexia nervosa and bulimia nervosa. We conducted a systematic review of the literature with the SPIDER search strategy assessing six databases. A meta-synthesis was performed with data from qualitative studies. Two independent reviewers screened and assessed the articles, extracted data from the articles and elaborated thematic synthesis. Nineteen articles met the inclusion/exclusion criteria. The meta-synthesis revealed three descriptive themes: Going outside the comfort zone: hard relational experiences of health professionals in providing care for people with anorexia nervosa and bulimia nervosa; Reflecting on treatment: relevance of discussion, communication, and flexibility in health professionals' work with anorexia nervosa and bulimia nervosa; and Dealing with ambivalences: experiences of health professionals with family members of people with anorexia nervosa and bulimia nervosa. We elaborated two analytical themes: Making work with eating disorders palatable: malleability necessary for health professionals in bonding with people with anorexia and bulimia nervosa and their families; and Leaving the professional comfort zone: transition from multi to interdisciplinary. Thus, mental health professionals who work with people diagnosed with anorexia and bulimia nervosa cope with hard emotional experiences that makes them feel out of their comfort zone, requiring flexibility to benefit a good therapeutic alliance, but there are still difficulties in promoting interdisciplinarity.


Assuntos
Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Anorexia Nervosa/terapia , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/psicologia , Bulimia Nervosa/terapia , Bulimia Nervosa/psicologia , Anorexia , Brasil
4.
Nitric Oxide ; 132: 15-26, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36736618

RESUMO

Spatial confinement and temporal regulation of signaling by nitric oxide (NO) and reactive oxygen species (ROS) occurs in cancer cells. Signaling mediated by NO and ROS was investigated in two sub clones of the murine melanoma B16F10-Nex2 cell line, Nex10C and Nex8H treated or not with bradykinin (BK). The sub clone Nex10C, similar to primary site cells, has a low capacity for colonizing the lungs, whereas the sub clone Nex8H, similar to metastatic cells, corresponds to a highly invasive melanoma. BK-treated Nex10C cells exhibited a transient increase in NO and an inhibition in basal O2- levels. Inhibition of endogenous NO production by l-NAME resulted in detectable levels of O2-. l-NAME promoted Rac1 activation and enhanced Rac1-PI3K association. l-NAME in the absence of BK resulted in Nex10C cell migration and invasion, suggesting that NO is a negative regulator of O2- mediated cell migration and cell invasion. BK-treated Nex8H cells sustained endogenous NO production through the activation of NOS3. NO activated Rac1 and promoted Rac1-PI3K association. NO stimulated cell migration and cell invasion through a signaling axis involving Ras, Rac1 and PI3K. In conclusion, a role for O2- and NO as positive regulators of Rac1-PI3K signaling associated with cell migration and cell invasion is proposed respectively for Nex10C and Nex8H murine melanoma cells.


Assuntos
Bradicinina , Melanoma , Camundongos , Animais , Bradicinina/farmacologia , Bradicinina/metabolismo , Superóxidos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Movimento Celular
5.
Cad Saude Publica ; 39(2): e00058022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36820737

RESUMO

The COVID-19 pandemic has led to a public health crisis, with increases in the number of deaths. As a result, the number of bereaved people has increased significantly. In addition, the measures adopted to control the spread of virus have triggered changes in the subjective and collective bereavement experiences. This systematic literature review aims to summarize and reinterpret the results of qualitative studies on the experience of losing family members during the pandemic by a thematic synthesis. The searches were performed in the Web of Science, Scopus, PubMed/MEDLINE, CINAHL, PsycINFO, and LILACS databases. Among 602 articles identified, 14 were included. Evidence was assessed using the Critical Appraisal Skills Programme tool. Two descriptive themes related to the objective were elaborated in addition to one analytical theme, namely: "Pandemic grief: lonely and unresolved". These themes proved to be interrelated and indicate that experiences of loss in this context were negatively impacted by the imperatives of physical distance, restriction of hospital visits, technology-mediated communication, and prohibition or restriction of funerals. These changes resulted in experiences marked by feelings of loneliness and helplessness, which should be considered when planning intervention strategies that favor communication between family members with the afflicted loved one and with the health care team, enabling welcoming and creating alternatives for farewell rituals. The findings may support further research to test intervention protocols, especially to guide public policies and promote psychological support to bereaved family members after their loss.


Assuntos
COVID-19 , Humanos , Pandemias , Brasil , Pesar , Família , Pesquisa Qualitativa
6.
Biomedicines ; 11(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36672704

RESUMO

Previous studies reported that p-coumaric acid modulates melanoma growth. Because the esterification of p-coumaric acid (p-CA) enhanced its activity as an antimelanogenic agent, we aimed to determine the antitumor potential of two derivatives, the ethyl and butyl esters, against the murine B16-F10 and the human SK-MEL-25 melanoma cells. Cell viability was determined in vitro by the lactate dehydrogenase release and violet crystal absorption assays. The cell proliferation rate and cell cycle behavior were determined by the colony formation assay and flow cytometry analysis. Although p-CA, at the concentration of 1 mM, failed to exert a significant antitumor activity, the ethyl and butyl ester derivatives caused substantial tumor cell death at doses < 1 mM. Despite a reduction in their direct cytotoxicity at minor doses, both products controlled the melanoma growth by arresting the cell cycle at the G0/G1 (B16-F10) or S/G2 (SK-MEL-25). Furthermore, the in vivo experiments showed that the butyl ester derivative suppressed the lung B16-F10 burden, compared to the p-CA-treated mice. Thus, the esterification of p-coumaric acid improved the control over the proliferation of murine and human melanoma cells and can be considered an approach for designing novel anticancer agents.

7.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 45(1): 62-70, Jan.-Feb. 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1420536

RESUMO

Objectives: To synthesize and reinterpret findings from primary qualitative studies on the emotional experience of health care professionals working with mental health and mental health professionals providing care for people with suicidal behavior. Methods: We conducted a systematic review of the literature with the SPIDER structured search strategy in six databases (PubMed, Web of Science, Scopus, PsycINFO, CINAHL, and LILACS). A meta-synthesis was performed with data from qualitative studies published between 2005 and 2021. Two independent reviewers screened and assessed the articles. They evaluated methodological quality of included articles, extracted data, and performed the thematic synthesis. Results: Of 852 articles, 21 met the inclusion/exclusion criteria and were synthesized. The meta-synthesis revealed three descriptive themes: coping with adverse experiences; coming across fortunate experiences; professional-personal implications. Based on these descriptive themes, we elaborated the analytical theme: bittersweet experiences of personal and professional transformation. Conclusions: Mental health professionals working with people manifesting suicidal behaviors must cope with complex emotional experiences that involve controversial and ambivalent feelings. Such feelings have repercussions that may transform personal and professional life. The present results are useful for the development and implementation of interventions that promote better overall mental health outcomes for healthcare providers. Registration number: PROSPERO CRD42021257237.

8.
Scand J Caring Sci ; 37(1): 20-36, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35781312

RESUMO

BACKGROUND: Body image is a multidimensional concept that involves the mental image of the human body and the feeling of being oneself throughout existence. Treatment for breast cancer causes several bodily changes that affect women's body image. AIMS: This meta-synthesis aims to synthesise and interpret primary qualitative studies on the experience of body image in women undergoing treatment for breast cancer. METHODS: A qualitative meta-synthesis was conducted employing systematic searches in six databases (PubMed, CINAHL, SCOPUS, Web of Science, PsycINFO, and LILACS). Data analysis was performed according to thematic synthesis. RESULTS: Forty studies were included. Five descriptive themes were identified: (1) actively saying goodbye to body image; (2) the rupture of body image; (3) the sacrifice of body image in exchange for life; (4) body image as a vehicle for social expression; and (5) resignation of the alterated body image. These themes were understood through one analytical theme: Half-woman: body image of the woman with breast cancer. CONCLUSION: The experience of body image in the context of breast cancer is a dynamic phenomenon, which involves dismissal, rupture, and resignation and occurs mediated by interpersonal contact.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Imagem Corporal , Pesquisa Qualitativa
9.
Braz J Psychiatry ; 45(1): 62-70, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35881567

RESUMO

OBJECTIVES: To synthesize and reinterpret findings from primary qualitative studies on the emotional experience of health care professionals working with mental health and mental health professionals providing care for people with suicidal behavior. METHODS: We conducted a systematic review of the literature with the SPIDER structured search strategy in six databases (PubMed, Web of Science, Scopus, PsycINFO, CINAHL, and LILACS). A meta-synthesis was performed with data from qualitative studies published between 2005 and 2021. Two independent reviewers screened and assessed the articles. They evaluated methodological quality of included articles, extracted data, and performed the thematic synthesis. RESULTS: Of 852 articles, 21 met the inclusion/exclusion criteria and were synthesized. The meta-synthesis revealed three descriptive themes: coping with adverse experiences; coming across fortunate experiences; professional-personal implications. Based on these descriptive themes, we elaborated the analytical theme: bittersweet experiences of personal and professional transformation. CONCLUSIONS: Mental health professionals working with people manifesting suicidal behaviors must cope with complex emotional experiences that involve controversial and ambivalent feelings. Such feelings have repercussions that may transform personal and professional life. The present results are useful for the development and implementation of interventions that promote better overall mental health outcomes for healthcare providers.


Assuntos
Pessoal de Saúde , Ideação Suicida , Humanos , Pesquisa Qualitativa , Pessoal de Saúde/psicologia , Saúde Mental , Adaptação Psicológica
10.
Cad. Saúde Pública (Online) ; 39(2): e00058022, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1421030

RESUMO

The COVID-19 pandemic has led to a public health crisis, with increases in the number of deaths. As a result, the number of bereaved people has increased significantly. In addition, the measures adopted to control the spread of virus have triggered changes in the subjective and collective bereavement experiences. This systematic literature review aims to summarize and reinterpret the results of qualitative studies on the experience of losing family members during the pandemic by a thematic synthesis. The searches were performed in the Web of Science, Scopus, PubMed/MEDLINE, CINAHL, PsycINFO, and LILACS databases. Among 602 articles identified, 14 were included. Evidence was assessed using the Critical Appraisal Skills Programme tool. Two descriptive themes related to the objective were elaborated in addition to one analytical theme, namely: "Pandemic grief: lonely and unresolved". These themes proved to be interrelated and indicate that experiences of loss in this context were negatively impacted by the imperatives of physical distance, restriction of hospital visits, technology-mediated communication, and prohibition or restriction of funerals. These changes resulted in experiences marked by feelings of loneliness and helplessness, which should be considered when planning intervention strategies that favor communication between family members with the afflicted loved one and with the health care team, enabling welcoming and creating alternatives for farewell rituals. The findings may support further research to test intervention protocols, especially to guide public policies and promote psychological support to bereaved family members after their loss.


A pandemia da COVID-19 causou uma crise de saúde pública com o aumento no número de mortes. Como resultado, o número de pessoas em luto aumentou significativamente. Além disso, as medidas adotadas com o objetivo de controlar a propagação do vírus desencadearam mudanças nas experiências subjetivas e coletivas de luto. Esta revisão sistemática da literatura teve como objetivo resumir e reinterpretar os resultados de estudos qualitativos sobre a experiência de luto devido à perda familiar durante a pandemia, por meio de uma síntese temática. As buscas foram feitas nas bases de dados Web of Science, Scopus, PubMed/MEDLINE, CINAHL, PsycINFO e LILACS. Dos 602 artigos identificados, 14 foram incluídos. As evidências foram avaliadas utilizando-se a ferramenta Critical Appraisal Skills Programme. Foram elaborados dois temas descritivos relacionados ao objetivo e um tema analítico, nomeado: "Luto pandêmico: solitário e inacabado". Esses temas mostraram-se inter-relacionados e indicam que, nesse contexto, as exigências de distância física, a restrição de visitas hospitalares, a comunicação mediada por tecnologia e a proibição ou restrição de rituais fúnebres impactaram negativamente as experiências de perda. Essas mudanças resultaram em experiências marcadas por sentimentos de solidão e desamparo, que devem ser consideradas no planejamento de estratégias de intervenção que favoreçam a comunicação entre os familiares e o ente querido acometido e com a equipe de saúde, possibilitando o acolhimento e a criação de alternativas para os rituais de despedida. Os resultados podem subsidiar novas pesquisas para testar protocolos de intervenção, especialmente para orientar políticas públicas e promover apoio psicológico ao familiar enlutado após a perda.


La pandemia de COVID-19 ha provocado una crisis de salud pública, con un aumento del número de muertes. Como consecuencia, el número de personas en duelo ha aumentado considerablemente. Además, las medidas adoptadas para controlar la propagación del virus han provocado cambios en las experiencias de duelo subjetivas y colectivas. Esta revisión sistemática de la literatura pretende resumir y reinterpretar los resultados de los estudios cualitativos sobre la experiencia de duelo por pérdida familiar durante la pandemia a través de una síntesis temática. Las búsquedas se realizaron en las bases de datos Web of Science, Scopus, PubMed/MEDLINE, CINAHL, PsycINFO y LILACS. De los 602 artículos identificados, se incluyeron 14. La evidencia se evaluó mediante la herramienta Critical Appraisal Skills Programme. Se elaboraron dos temas descriptivos relacionados con el objetivo y un tema analítico, a saber: "Duelo pandémico: solitario e inacabado". Estos temas resultaron estar interrelacionados e indican que las experiencias de pérdida en este contexto se vieron negativamente afectadas por los imperativos de la distancia física, la restricción de las visitas al hospital, la comunicación mediada por la tecnología y la prohibición o restricción de los rituales funerarios. Estos cambios se tradujeron en experiencias marcadas por sentimientos de soledad y desamparo, que deben tenerse en cuenta a la hora de planificar estrategias de intervención que favorezcan la comunicación de los familiares con el familiar afectado y con el equipo sanitario, posibilitando la acogida y creando alternativas para los rituales de despedida. Los resultados pueden respaldar nuevas investigaciones para probar protocolos de intervención, especialmente para orientar las políticas públicas y promover el apoyo psicológico al familiar en duelo tras la pérdida.

11.
Cad. Saúde Pública (Online) ; 39(7): e00223122, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1447792

RESUMO

Abstract: This study sought to synthesize and reinterpret findings from primary qualitative studies on the experience of health professionals in caring for people with anorexia nervosa and bulimia nervosa. We conducted a systematic review of the literature with the SPIDER search strategy assessing six databases. A meta-synthesis was performed with data from qualitative studies. Two independent reviewers screened and assessed the articles, extracted data from the articles and elaborated thematic synthesis. Nineteen articles met the inclusion/exclusion criteria. The meta-synthesis revealed three descriptive themes: Going outside the comfort zone: hard relational experiences of health professionals in providing care for people with anorexia nervosa and bulimia nervosa; Reflecting on treatment: relevance of discussion, communication, and flexibility in health professionals' work with anorexia nervosa and bulimia nervosa; and Dealing with ambivalences: experiences of health professionals with family members of people with anorexia nervosa and bulimia nervosa. We elaborated two analytical themes: Making work with eating disorders palatable: malleability necessary for health professionals in bonding with people with anorexia and bulimia nervosa and their families; and Leaving the professional comfort zone: transition from multi to interdisciplinary. Thus, mental health professionals who work with people diagnosed with anorexia and bulimia nervosa cope with hard emotional experiences that makes them feel out of their comfort zone, requiring flexibility to benefit a good therapeutic alliance, but there are still difficulties in promoting interdisciplinarity.


Resumo: Este estudo buscou sintetizar e reinterpretar os achados de estudos qualitativos primários sobre a experiência de profissionais de saúde no cuidado a pessoas com anorexia e bulimia nervosa. Realizamos uma revisão sistemática da literatura com a estratégia de busca estruturada SPIDER em seis bases de dados. Foi realizada uma metassíntese com dados destes estudos qualitativos. Os artigos foram triados e avaliados por dois revisores independentes que extraíram dados desses artigos e elaboraram uma síntese temática. No total, 19 artigos atenderam nossos critérios de inclusão e exclusão. A metassíntese revelou três temas descritivos: Sair da zona de conforto: profissionais de saúde tiveram vivências relacionais difíceis no cuidado à pessoa com anorexia e bulimia nervosa; Refletir sobre o tratamento: a relevância da discussão, comunicação e flexibilidade no trabalho dos profissionais de saúde; e Lidar com ambivalências: vivências de profissionais de saúde com familiares de pessoas com anorexia e bulimia nervosa. Elaboramos dois temas analíticos: Tornando o trabalho com distúrbios alimentares agradável: maleabilidade necessária para vincular profissionais de saúde à pessoa com anorexia e bulimia nervosa e sua família; e Saindo da zona de conforto profissional: transição do multi para o interdisciplinar. Assim, os profissionais de saúde mental que trabalham com pessoas diagnosticadas com anorexia e bulimia nervosa enfrentam experiências emocionais difíceis que os fazem se sentir fora de sua zona de conforto, exigindo flexibilidade para o benefício de uma boa aliança terapêutica, mas ainda há dificuldades em promover a interdisciplinaridade.


Resumen: Este estudio buscó sintetizar y reinterpretar los hallazgos de estudios cualitativos primarios sobre la experiencia de profesionales de la salud en el cuidado de personas con anorexia y bulimia nerviosa. Realizamos una revisión sistemática de la literatura con la estrategia de búsqueda estructurada SPIDER en seis bases de datos. Se realizó una metasíntesis con los datos de estos estudios cualitativos. Los artículos fueron seleccionados y evaluados por dos revisores independientes que extrajeron datos de estos artículos y elaboraron una síntesis temática. En total, 19 artículos cumplieron con nuestros criterios de inclusión y exclusión. La metasíntesis reveló tres temas descriptivos: Salir de la zona de confort: los profesionales de la salud tuvieron vivencias relacionales difíciles en el cuidado a la persona con anorexia y bulimia nerviosa; Reflexionar sobre el tratamiento: la relevancia de la discusión, la comunicación y la flexibilidad en el trabajo de los profesionales de la salud; y Lidiar con las ambivalencias: experiencias de los profesionales de la salud con familiares de personas con anorexia y bulimia nerviosa. Elaboramos dos temas analíticos: Hacer agradable el trabajo con los trastornos alimentarios: maleabilidad necesaria para vincular a los profesionales de la salud con la persona con anorexia y bulimia nerviosa y su familia; y Salir de la zona de confort profesional: transición de lo múltiple a lo interdisciplinario. Por lo tanto, los profesionales de la salud mental que trabajan con personas diagnosticadas con anorexia y bulimia nerviosa enfrentan experiencias emocionales difíciles que los hacen sentir fuera de su zona de confort, lo que requiere flexibilidad en beneficio de una buena alianza terapéutica, pero aún existen dificultades para promover la interdisciplinariedad.

12.
Nanomaterials (Basel) ; 12(18)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36144933

RESUMO

Inflammasomes are cytosolic complexes composed of a Nod-like receptor, NLR, the adaptor protein, ASC, and a proteolytic enzyme, caspase-1. Inflammasome activation leads to caspase-1 activation and promotes functional maturation of IL-1ß and IL-18, two prototypical inflammatory cytokines. Besides, inflammasome activation leads to pyroptosis, an inflammatory type of cell death. Inflammasomes are vital for the host to cope with foreign pathogens or tissue damage. Herein, we show that quantum-dot-based iron oxide nanoparticles, MNP@QD, trigger NLRP3 inflammasome activation and subsequent release of proinflammatory interleukin IL-1ß by murine bone marrow-derived dendritic cells (BMDCs). This activation is more pronounced if these cells endocytose the nanoparticles before receiving inflammatory stimulation. MNP@QD was characterized by using imaging techniques like transmission electron microscopy, fluorescence microscopy, and atomic force microscopy, as well as physical and spectroscopical techniques such as fluorescence spectroscopy and powder diffraction. These findings may open the possibility of using the composite MNP@QD as both an imaging and a therapeutic tool.

13.
Sci Rep ; 12(1): 13636, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948616

RESUMO

Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-ß gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-ß gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.


Assuntos
Cardiotoxicidade , Neoplasias , Cardiotoxicidade/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Genes Neoplásicos , Humanos , Imunoterapia/métodos , Interferon beta/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética
14.
Viruses ; 14(4)2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35458405

RESUMO

The new betacoronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the cause of COVID-19, and has spread rapidly around the world, reaching more than 200 countries, around 364 million people and causing more than 5 million deaths according to the World Health Organization, so this paper reports a fatal case of SARS-CoV-2 infection in a young pregnant woman with heart disease, without vertical transmission. A 26 years old patient at 28th week of pregnancy with regular prenatal care, presented dry cough, high fever, and severe respiratory distress. Due to her clinical symptoms, she sought medical care at a cardiology hospital in Northern Brazil. The medical conditions she presented were heart disease, rheumatic fever history and had no recent record of national or international travel. She was hospitalized and after clinical stabilization, she was referred for an emergency cesarean intervention. The young mother and the newborn were transferred to the intensive care unit after surgery, where diagnostic tests for respiratory viral infections, including SARS-CoV-2, were performed. The mother tested positive, while her newborn was negative for SARS-CoV-2 demonstrating no vertical transmission of SARS-CoV-2 in this severe case. This study reveals that despite the mother's initially mild symptoms, she progressed to severe clinical conditions resulting in death, although no vertical transmission was observed. This report highlights the relevance of comorbidities for the unfavorable clinical course of COVID-19.


Assuntos
COVID-19 , Cardiopatias , Complicações Infecciosas na Gravidez , Adulto , COVID-19/diagnóstico , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , SARS-CoV-2
15.
Estud. Psicol. (Campinas, Online) ; 39: e200221, 2022. tab, graf
Artigo em Inglês | LILACS, Index Psicologia - Periódicos | ID: biblio-1404758

RESUMO

Masculinity is a construct associated with cisgender men; however, transgender men also perform masculinities. This study aimed to synthesize, analyze, and reinterpret the findings of primary qualitative studies about transgender men's experience of masculinity. The research question developed through the SPIDER strategy was: What is the qualitative evidence of masculinity performed by transgender men? Eighteen studies involving over 200 transgender men between the ages of 19 and 65 were selected. Three descriptive themes emerged: "Bodily performance of masculinity," "Social performances of masculinity," and "Sexualities." Analytical themes were generated: "The appearance of masculinity" and "Far beyond appearance". The results point to complementary experiences of masculinity: concerning physical appearance and body modifications; and the practices contesting the hegemonic masculinity standard. The experience of masculinities is outlined by body changes, culminating in the passability and social recognition of the transgender man.


A masculinidade é um constructo associado aos homens cisgêneros; entretanto, homens transgêneros também performam masculinidades. O objetivo deste estudo foi sintetizar, analisar e reinterpretar os achados dos estudos qualitativos primários acerca da experiência da masculinidade de homens transgêneros. A questão de pesquisa, desenvolvida por meio da estratégia SPIDER, foi: Quais são as evidências qualitativas da experiência da masculinidade performada por homens transgêneros? Foram selecionados 18 estudos que envolveram mais de 200 homens transgêneros com idades entre 19 e 65 anos. Emergiram três temas descritivos: "Performances corporais da masculinidade", "Performances sociais da masculinidade" e "Sexualidades". Foram gerados os temas analíticos: "A aparência da masculinidade" e "Muito além da aparência". Os resultados apontam para experiências de masculinidade complementares: relativas à aparência física e às modificações corporais e às práticas contestadoras do padrão de masculinidade hegemônica. A vivência das masculinidades é delineada pelas alterações corporais, culminando na passabilidade e no reconhecimento social do homem transgênero.


Assuntos
Transexualidade , Masculinidade , Pessoas Transgênero , Identidade de Gênero
16.
Cancer Invest ; 39(8): 607-620, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33826457

RESUMO

Gynecological cancers have an impact on women's psychosexual health in which results vary from adjuvant cancer therapy, such as loss of pleasure, to anxious symptoms. This study aimed to present a meta-synthesis of qualitative primary studies on the sexual experience of women with gynecological cancer. The SPIDER tool and the PRISMA guidelines were used to recover evidence from the databases Web of Science, SCOPUS, PubMed/MedLine, CINAHL, PsycINFO and LILACS. Twenty articles were included. The thematic synthesis showed that alterations in sexual functions can be mitigated by direct involvement and dialogue with a sexual partner and the resignification of sexual intimacy.


Assuntos
Neoplasias dos Genitais Femininos/psicologia , Sexualidade/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , Adulto Jovem
17.
J Inorg Biochem ; 215: 111314, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33261934

RESUMO

Neurotoxicity of amyloid beta (Aß) species generated in early stages of aggregation has been associated with development of Alzheimer's disease (AD). Consequently, the field of action of compounds that can identify and inhibit the formation of these species has enlarged considerably. This study investigates the effect and influence of the luminescent, water soluble metal complex cis-[Ru(phen)2(3,4Apy)2]2+ (RuApy, 3,4Apy = 3,4-diaminopyridine, phen = 1,10-phenanthroline) on the aggregation process and toxicity of Aß1-40 and its Aß1-28, Aß11-22 and Aß29-40 fragments since their early stages. The absence of correlation between the conformations generated by Aß fragments and the full length 1-40 peptide during aggregation and the absence of toxicity of Aß fragments to PC12 cells in all stages of aggregation indicated that the aggregation pathway and toxicity found to the full-length Aß1-40 depends on specific interactions between the three fragments. The toxicity of Aß1-40 was dependent on the aggregation step investigated: species generated at the beginning (15 min) of aggregation were toxic, whereas mature (120 min) fibrils were not. The RuApy complex is not toxic to PC12 cells up to 60 µM, and does not interfere with the aggregation pathway of the Aß fragments, but interferes with the aggregation of Aß1-40 and protects the PC12 cells, maintaining 100% of cell viability against the toxicity of Aß1-40 species generated in early stages of aggregation.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Complexos de Coordenação/farmacologia , Agregação Patológica de Proteínas/metabolismo , Rutênio/farmacologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Microscopia Eletrônica de Transmissão , Células PC12 , Fragmentos de Peptídeos/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Agregação Patológica de Proteínas/patologia , Ratos , Rutênio/química , Solubilidade , Água/química
18.
Oxid Med Cell Longev ; 2019: 5719483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285786

RESUMO

Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Etanol/química , Melanoma Experimental/tratamento farmacológico , Melanoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Senna/química , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Masculino , Melanoma/metabolismo , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Neoplasias Cutâneas/metabolismo , Melanoma Maligno Cutâneo
19.
Nitric Oxide ; 89: 1-13, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009708

RESUMO

Cancer development is closely related to chronic inflammation, which is associated with identifiable markers of tumor progression, such as uncontrolled cell proliferation, angiogenesis, genomic instability, chemotherapeutic resistance, and metastases. Redox processes mediated by reactive oxygen species (ROS) and nitric oxide (NO) within the inflammatory tumor microenvironment play an essential role in directly influencing intercellular and intracellular signaling. These reactive species originating in the cancer cell or its microenvironment, mediate the epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET). However, intracellular interactions between NO and ROS must be controlled to prevent cell death. Melanoma, breast, and colon cancer cells have developed a mechanism to survive and adapt to oxidative and nitrosative stress. The mechanism involves a spatial-temporal fine adjustment of the intracellular concentrations of NO and ROS, thereby guaranteeing the successful development of cancer cells. Physiological concentrations of NO and supra physiological concentrations of ROS are prevalent in cancer cells at the primary site. The situation reverses in cancer cells undergoing the EMT prior to being released into the blood stream. Intracellular supra physiological concentrations of NO found in circulating cancer cells endow them with anoikis resistance. When the anoikis-resistant cancer cells arrive at a metastatic site they undergo the MET. Endogenous supra physiological concentrations of ROS and physiological NO concentrations are prevalent in these cells. Understanding tumor progression from the perspective of redox signaling permits the characterization of new markers and approaches to therapy. The synthesis and use of compounds with the capacity of modifying intracellular concentrations of NO and ROS may prove effective in disrupting a redox homeostasis operative in cancer cells.


Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias do Colo/fisiopatologia , Melanoma/fisiopatologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Melanoma/tratamento farmacológico , Doadores de Óxido Nítrico/uso terapêutico , Microambiente Tumoral/fisiologia
20.
J Integr Med ; 17(2): 132-140, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30799248

RESUMO

OBJECTIVE: Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its root. This study aimed to evaluate the cytotoxicity and antitumor effects of the crude extract of A. archangelica root (CEAA) on breast cancer. METHODS: The cytotoxicity of CEAA against breast adenocarcinoma cells (4T1 and MCF-7) was evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Morphological and biochemical changes were detected by Hoechst 33342/propidium iodide (PI) and annexin V/PI staining. Cytosolic calcium mobilization was evaluated in cells staining with FURA-4NW. Immunoblotting was used to determine the effect of CEAA on anti- and pro-apoptotic proteins (Bcl-2 and Bax, respectively). The 4T1 cell-challenged mice were used for in vivo assay. RESULTS: Using ultra-high-performance liquid chromatography-mass spectrometry analysis, angelicin, a constituent of the roots and leaves of A. archangelica, was found to be the major constituent of the CEAA evaluated in this study (73 µg/mL). The CEAA was cytotoxic for both breast cancer cell lines studied but not for human fibroblasts. Treatment of 4T1 cells with the CEAA increased Bax protein levels accompanied by decreased Bcl-2 expression, in the presence of cleaved caspase-3 and cytosolic calcium mobilization, suggesting mitochondrial involvement in breast cancer cell death induced by the CEAA in this cell line. No changes on the Bcl-2/Bax ratio were observed in CEAA-treated MCF7 cells. Gavage administration of the CEAA (500 mg/kg) to 4T1 cell-challenged mice significantly decreased tumor growth when compared with untreated animals. CONCLUSION: Altogether, our data show the antitumor potential of the CEAA against breast cancer cells in vitro and in vivo. Further research is necessary to better elucidate the pharmacological application of the CEAA in breast cancer therapy.


Assuntos
Angelica archangelica/química , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/fisiopatologia , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Rizoma/química , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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