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BACKGROUND: Cancer treatment has many side effects; therefore, more efficient treatments are needed. Mesenchymal stem cells (MSC) have immunoregulatory properties, tumor site migration and can be genetically modified. Some proteins, such as soluble TRAIL (sTRAIL) and interleukin-12 (IL-12), have shown antitumoral potential, thus its combination in solid tumors could increase their activity. MATERIALS AND METHODS: Lentiviral transduction of bone marrow MSC with green fluorescent protein (GFP) and transgenes (sTRAIL and IL-12) was confirmed by fluorescence microscopy and Western blot. Soluble TRAIL levels were quantified by ELISA. Lymphoma L5178Y cells express a reporter gene (GFP/mCherry), and TRAIL receptor (DR5). RESULTS: An in vivo model showed that combined treatment with MSC expressing sTRAIL+IL-12 or IL-12 alone significantly reduced tumor volume and increased survival in BALB/c mice (p < 0.05) with only one application. However, at the histological level, only MSC expressing IL-12 reduced tumor cell infiltration significantly in the right gastrocnemius compared with the control group (p < 0.05). It presented less tissue dysplasia confirmed by fluorescence and hematoxylin-eosin dye; nevertheless, treatment not inhibited hepatic metastasis. CONCLUSIONS: MSC expressing IL-12, is or combination with BM-MSC expressing sTRAIL represents an antitumor strategy for lymphoma tumors since they increase survival and reduce tumor development. However, the combination did not show significative additive effect. The localized application did not inhibit metastasis but reduced morphological alterations of tissue associated with liver metastasis.

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INTRODUCTION: More than half of all worldwide deaths and disabilities were caused by stroke. Large artery atherosclerosis is identified as a high etiological risk factor because it accounts for 20% of ischemic stroke. OBJECTIVES: To identify the significance of TRAIL and adropin release and the relative changes related to S100B levels, as well as the relationship between these biomarkers and the final infarct core, the clinical outcome, and the presence of large artery atherosclerosis in acute stroke patients. MATERIALS AND METHODS: Over a one-year period, demographic, clinical, and neuroimaging findings of 90 consecutive patients with acute ischemic stroke were evaluated. RESULTS: The mean age of participants was 69.28 ± 10 and 39 patients were female. The increased level of S100B and the decreased levels of sTRAIL with adropin were significantly associated with moderate to severe neurologic presentation (p=0.0001, p=0.002, p=0.002, respectively). On the control CT, a large infarct core was significantly associated with decreased serum levels of sTRAIL and adropin (p=0.001 and p=0.000, respectively); however, the levels of S100B were not significantly associated with good ASPECTS score (p=0.684). Disability and an unfavorable outcome were significantly related to the decreased level of sTRAIL and adropin (p=0.001 and p=0.000 for THRIVE score>5, respectively). Decreased sTRAIL and adropin levels and an increased S100B level were correlated with the presence of large artery atherosclerotic etiologic factors (p=0.000, p=0.000, p=0.036, respectively). CONCLUSION: TRAIL and adropin serum levels were associated with poor clinical outcomes and greater infarcted area in acute ischemic stroke patients.

Introducción. Más de la mitad de todas las muertes y discapacidades en todo el mundo fueron causadas por accidentes cerebrovasculares. La aterosclerosis de las grandes arterias se identifica como un factor de alto riesgo etiológico debido a que representa el 20 % de los accidentes cerebrovasculares isquémicos. Objetivo. Determinar la importancia de la liberación de TRAIL y adropina y los cambios relativos relacionados con los niveles de S100B, así como la relación entre estos biomarcadores y el núcleo final del infarto, el resultado clínico y la presencia de aterosclerosis de arterias grandes en pacientes con accidente cerebrovascular agudo. Materiales y métodos. Durante un año, se evaluaron los hallazgos demográficos, clínicos y de neuroimágenes de 90 pacientes con accidente cerebrovascular isquémico agudo. Resultados. La edad media de los pacientes fue de 69,28 ± 10 y 39 eran mujeres. El aumento del nivel de S100B y la disminución de los niveles de sTRAIL y adropina se asociaron significativamente con una presentación neurológica moderada a grave en los pacientes (p=0,0001, p=0,002 y p=0,002, respectivamente). En la TC de control, un gran núcleo de infarto se asoció significativamente con una disminución del nivel sérico de sTRAIL y adropina (p=0,001 y p=0,000, respectivamente); sin embargo, los niveles de S100B no se asociaron significativamente con una buena puntuación en el ASPECT (p=0,684). La discapacidad y el resultado desfavorable se relacionaron significativamente con la disminución de los niveles de sTRAIL y adropina (p=0,001 y p=0,000 para una puntuación >5 en el THRIVE, respectivamente). La disminución de los niveles de sTRAIL y adropina y el aumento del nivel de S100B, se correlacionaron con la presencia de un factor etiológico aterosclerótico de arterias grandes entre la población de estudio (p=0,000, p=0,000 y p=0,036, respectivamente). Conclusiones. Los niveles séricos de TRAIL y adropina se asociaron con un resultado clínico deficiente y una mayor área infartada en pacientes con ataque cerebrovascular isquémico agudo.

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Introduction: More than half of all worldwide deaths and disabilities were caused by stroke. Large artery atherosclerosis is identified as a high etiological risk factor because it accounts for 20% of ischemic stroke. Objectives: To identify the significance of TRAIL and adropin release and the relative changes related to S100B levels, as well as the relationship between these biomarkers and the final infarct core, the clinical outcome, and the presence of large artery atherosclerosis in acute stroke patients. Materials and methods: Over a one-year period, demographic, clinical, and neuroimaging findings of 90 consecutive patients with acute ischemic stroke were evaluated. Results: The mean age of participants was 69.28 ± 10 and 39 patients were female. The increased level of S100B and the decreased levels of sTRAIL with adropin were significantly associated with moderate to severe neurologic presentation (p=0.0001, p=0.002, p=0.002, respectively). On the control CT, a large infarct core was significantly associated with decreased serum levels of sTRAIL and adropin (p=0.001 and p=0.000, respectively); however, the levels of S100B were not significantly associated with good ASPECTS score (p=0.684). Disability and an unfavorable outcome were significantly related to the decreased level of sTRAIL and adropin (p=0.001 and p=0.000 for THRIVE score>5, respectively). Decreased sTRAIL and adropin levels and an increased S100B level were correlated with the presence of large artery atherosclerotic etiologic factors (p=0.000, p=0.000, p=0.036, respectively). Conclusion: TRAIL and adropin serum levels were associated with poor clinical outcomes and greater infarcted area in acute ischemic stroke patients.

Introducción. Más de la mitad de todas las muertes y discapacidades en todo el mundo fueron causadas por accidentes cerebrovasculares. La aterosclerosis de las grandes arterias se identifica como un factor de alto riesgo etiológico debido a que representa el 20 % de los accidentes cerebrovasculares isquémicos. Objetivo. Determinar la importancia de la liberación de TRAIL y adropina y los cambios relativos relacionados con los niveles de S100B, así como la relación entre estos biomarcadores y el núcleo final del infarto, el resultado clínico y la presencia de aterosclerosis de arterias grandes en pacientes con accidente cerebrovascular agudo. Materiales y métodos. Durante un año, se evaluaron los hallazgos demográficos, clínicos y de neuroimágenes de 90 pacientes con accidente cerebrovascular isquémico agudo. Resultados. La edad media de los pacientes fue de 69,28 ± 10 y 39 eran mujeres. El aumento del nivel de S100B y la disminución de los niveles de sTRAIL y adropina se asociaron significativamente con una presentación neurológica moderada a grave en los pacientes (p=0,0001, p=0,002 y p=0,002, respectivamente). En la TC de control, un gran núcleo de infarto se asoció significativamente con una disminución del nivel sérico de sTRAIL y adropina (p=0,001 y p=0,000, respectivamente); sin embargo, los niveles de S100B no se asociaron significativamente con una buena puntuación en el ASPECT (p=0,684). La discapacidad y el resultado desfavorable se relacionaron significativamente con la disminución de los niveles de sTRAIL y adropina (p=0,001 y p=0,000 para una puntuación >5 en el THRIVE, respectivamente). La disminución de los niveles de sTRAIL y adropina y el aumento del nivel de S100B, se correlacionaron con la presencia de un factor etiológico aterosclerótico de arterias grandes entre la población de estudio (p=0,000, p=0,000 y p=0,036, respectivamente). Conclusiones. Los niveles séricos de TRAIL y adropina se asociaron con un resultado clínico deficiente y una mayor área infartada en pacientes con ataque cerebrovascular isquémico agudo.

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Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion.

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