A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate.

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.

Lonomia obliqua Venom Induces NF-κB Activation and a Pro-Inflammatory Profile in THP-1-Derived Macrophage.

Envenomation caused by contact with Lonomia obliqua bristles is characterized by pain, an intense systemic proinflammatory reaction and disturbances in the coagulation cascade that can cause severe clinical manifestations and death. However, the role of immune system components in these effects is still poorly understood. In this study, we evaluated the cytotoxic effect of L. obliqua venom on THP-1-derived macrophages and its ability to modulate inflammatory markers, as well as the cytokine and chemokine release profile. Our results show that L. obliqua venom is able to directly exert a potent pro-inflammatory reaction in macrophages, characterized by the activation of the NF-κB transcription factor pathway, the expression of CD80 and CD83, and the release of pro-inflammatory mediators such as TNF-α, IL-1ß, IL-6, IL-8 and CXCL10. These results suggest that macrophages can play an important role during the orchestration of the inflammatory response present in envenomation caused by Lonomia obliqua caterpillars.

Lonomia obliqua venom induces NF-κB activation and a pro-inflammatory profile in THP-1-derived macrophage

Envenomation caused by contact with Lonomia obliqua bristles is characterized by pain, an intense systemic proinflammatory reaction and disturbances in the coagulation cascade that can cause severe clinical manifestations and death. However, the role of immune system components in these effects is still poorly understood. In this study, we evaluated the cytotoxic effect of L. obliqua venom on THP-1-derived macrophages and its ability to modulate inflammatory markers, as well as the cytokine and chemokine release profile. Our results show that L. obliqua venom is able to directly exert a potent pro-inflammatory reaction in macrophages, characterized by the activation of the NF-κB transcription factor pathway, the expression of CD80 and CD83, and the release of pro-inflammatory mediators such as TNF-α, IL-1β, IL-6, IL-8 and CXCL10. These results suggest that macrophages can play an important role during the orchestration of the inflammatory response present in envenomation caused by Lonomia obliqua caterpillars.

Impacto psicossocial e comportamental da alergia alimentar em crianças, adolescentes e seus familiares: uma revisão / Psychosocial and behavioral impact of food allergies on children, adolescents and their families: a review

Objetivo: Analisar as evidências da literatura sobre a relação entre alergia alimentar infantil e o impacto psicossocial e comportamental em crianças, adolescentes e seus familiares. Método: Realizou-se uma busca bibliográfica nas seguintes bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), National Center for Biotechnology Information (PubMed) e na biblioteca eletrônica Scientific Electronic Library On-line (SciELO), com foco em artigos publicados no período de 1995 a 2017, em português e/ou inglês. Os descritores utilizados foram: food allergy, children, anxiety, feeding disorders e quality of life. Resultados: A prevalência das doenças alérgicas tem aumentado nas últimas décadas, sobretudo entre as crianças, com impacto significativo sobre os aspectos da vida diária e qualidade de vida tanto da criança quanto da família. Ansiedade, faltas escolares e bullying têm maior incidência em crianças com alergia alimentar. Quanto aos cuidadores, há maior prevalência de estresse, depressão e isolamento por medo de exposição a alérgenos. Conclusão: É possível verificar uma relação entre alergias alimentares em crianças e uma piora da qualidade de vida. Ademais, as dificuldades alimentares advindas de alergias (motoras, neofobias e preferências alimentares) podem prejudicar o desenvolvimento e crescimento das crianças. É necessário o acompanhamento por equipe multiprofissional especializada e treinada, além de mais estudos que abordem novas estratégias e técnicas específicas para o tratamento desta população.

Objective: To analyze evidence available in the literature on the relationship between food allergies in children and their psychosocial and behavioral impact on the patients (children or adolescents) and their families. Method: A literature search was conducted in the following databases: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), National Center for Biotechnology Information (PubMed), and Scientific Electronic Library Online (SciELO), browsing for articles published between 1995 and 2017, in Portuguese and/or English. The following descriptors were used: food allergy, children, anxiety, feeding disorders, and quality of life. Results: The prevalence of allergic diseases has increased over the past few decades, especially among children, with significant impact on daily living and quality of life of both the child and the family. Anxiety, school absenteeism and bullying have higher incidence rates in children with food allergies. Among caregivers, higher prevalence rates of stress, depression and isolation for fear of exposure to allergens were observed. Conclusion: It is possible to identify a relationship between food allergies in children and worse quality of life. Furthermore, the difficulties resulting from food allergies (motor skills, food neophobia and food preferences) may affect the children's development and growth. Follow-up by a specialized, trained multidisciplinary team is required, as are further studies addressing new strategies and techniques specifically designed for the treatment of this population.

Axially-modified paddlewheel diruthenium(II,III)-ibuprofenato metallodrugs and the influence of the structural modification on U87MG and A172 human glioma cell proliferation, apoptosis, mitosis and migration.

The metallodrug chloridotetrakis(ibuprofenato)diruthenium(II,III) ([Ru2(Ibp)4Cl] or RuIbpCl (1), Ibp=carboxylate anion derived from the non-steroidal anti-inflammatory drug ibuprofen) has shown promising results in vitro and in vivo, which point to its potential as an inhibitor of glioma tumour growth in vivo. In order to get insight into the influence of structural changes on the biological response of the metallodrug, the [Ru2(Ibp)4] metal-metal multiply bonded paddlewheel unit was modified for the axial ligand. Two new analogues, [Ru2(Ibp)4(CF3SO3)] (2) and [Ru2(Ibp)4(EtOH)2]PF6 (3), were synthesized and fully characterized by elemental analysis, ESI-MS, vibrational (FTIR, Raman) and electronic (UV/VIS/NIR) spectroscopy, magnetic susceptibility, molar conductivity measurements, and thermal analysis. RuIbpCl was re-prepared and complementary characterization to previous work was performed. The three axially-modified RuIbp metallodrugs were compared for their effects on U87MG and A172 human glioma cell proliferation, apoptosis, mitosis, and cell migration in vitro. The results provide evidence that the chloride ligand in RuIbpCl may play key role in the mode of action of the metallodrug, since the best results for antiproliferative activity were found for (1) in both types of human glioma cells. All the metallodrugs, (1), (2) and (3), were uptaken by the cells, and were shown to cause increase on number of apoptotic cells and decrease on number of mitotic cells. Additionally, the RuIbp metallodrugs were capable of inhibiting cell migration process in both human glioma cell lines. These data are extremely promising as drugs which can inhibit both cell proliferation/mitosis and inhibit cell migration could target two major chemotherapeutic targets in high grade gliomas.

E series prostaglandins alter the proliferative, apoptotic and migratory properties of T98G human glioma cells in vitro.

BACKGROUND: In many types of cancer, prostaglandin E2 (PGE2) is associated with tumour related processes including proliferation, migration, angiogenesis and apoptosis. However in gliomas the role of this prostanoid is poorly understood. Here, we report on the proliferative, migratory, and apoptotic effects of PGE(1), PGE(2) and Ibuprofen (IBP) observed in the T98G human glioma cell line in vitro. METHODS: T98G human glioma cells were treated with IBP, PGE(1) or PGE(2) at varying concentrations for 24-72 hours. Cell proliferation, mitotic index and apoptotic index were determined for each treatment. Caspase-9 and caspase-3 activity was measured using fluorescent probes in live cells (FITC-LEHD-FMK and FITC-DEVD-FMK respectively). The migratory capacity of the cells was quantified using a scratch migration assay and a transwell migration assay. RESULTS: A significant decrease was seen in cell number (54%) in the presence of 50 µM IBP. Mitotic index and bromodeoxyuridine (BrdU) incorporation were also decreased 57% and 65%, respectively, by IBP. The apoptotic index was increased (167%) and the in situ activity of caspase-9 and caspase-3 was evident in IBP treated cells. The inhibition of COX activity by IBP also caused a significant inhibition of cell migration in the monolayer scratch assay (74%) and the transwell migration assay (36%). In contrast, the presence of exogenous PGE(1) or PGE(2) caused significant increases in cell number (37% PGE(1) and 45% PGE(2)). When mitotic index was measured no change was found for either PG treatment. However, the BrdU incorporation rate was significantly increased by PGE(1) (62%) and to a greater extent by PGE(2) (100%). The apoptotic index was unchanged by exogenous PGs. The addition of exogenous PGs caused an increase in cell migration in the monolayer scratch assay (43% PGE(1) and 44% PGE(2)) and the transwell migration assay (28% PGE(1) and 68% PGE(2)). CONCLUSIONS: The present study demonstrated that treatments which alter PGE(1) and PGE(2) metabolism influence the proliferative and apoptotic indices of T98G glioma cells. The migratory capacity of the cells was also significantly affected by the change in prostaglandin metabolism. Modifying PG metabolism remains an interesting target for future studies in gliomas.