ABSTRACT
Bovine lactoferrin (bLf) is a milk-derived protein that exhibits potent broad-spectrum antifungal activity against multiple fungi. bLf is susceptible to degradation, while some of its properties depend on the tertiary structure. So, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added value to enhance its biological activities. Plasmonic magnetoliposomes (PMLs) arise as promising nanocarriers for dual hyperthermia (magneto-photothermia) and local chemotherapy, since the combination of magnetic and gold nanoparticles (NPs) in a single nanosystem (multifunctional liposomes) enables the targeting and controlled release of loaded drugs. In this work, plasmonic magnetoliposomes (PMLs) containing manganese ferrite nanoparticles (28 nm size) and gold nanoparticles (5-7.5 nm size), functionalized with 11-mercaptoundecanoic acid or octadecanethiol, were prepared and loaded with bLf. The NPs' optical, magnetic and structural properties were measured via UV/vis/NIR absorption spectroscopy, SQUID and TEM, respectively. The Specific Absorption Rate (SAR) was calculated to assess the capabilities for magnetic and photothermal hyperthermia. Finally, the antifungal potential of bLf-loaded PMLs and their mechanism of internalization were assessed in Saccharomyces cerevisiae by counting the colony forming units and using fluorescence microscopy. The results demonstrate that PMLs are mainly internalized through an energy- and temperature-dependent endocytic process, though the contribution of a diffusion component cannot be discarded. Most notably, only bLf-loaded plasmonic magnetoliposomes display cytotoxicity with an efficiency similar to free bLf, attesting their promising potential for bLf delivery in the context of antifungal therapeutic interventions.
ABSTRACT
BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.
Subject(s)
Breast Neoplasms/pathology , Curcumin/pharmacology , Disease Progression , Naphthoquinones/pharmacology , Breast Neoplasms/blood supply , Breast Neoplasms/drug therapy , Cell Adhesion/drug effects , Cell Movement/drug effects , Cell Survival/drug effects , Curcumin/chemistry , Curcumin/therapeutic use , Extracellular Matrix/metabolism , Female , Humans , MCF-7 Cells , Naphthoquinones/chemistry , Neoplasm Invasiveness , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/metabolismABSTRACT
A novel experiment has been developed with a goal of enhancing engagement and deepening understanding of fundamental molecular biology concepts. In this laboratory activity, students investigate the composition of pet foods through quantitative polymerase chain reaction (qPCR) analysis. By conducting this experiment, students address a scientific question that has the potential to be of personal interest and they gain an appreciation of the power of genetic analysis. To develop this activity, ingredient lists of popular pet foods were surveyed and eight different components were selected to be the subject of inquiry. Reaction conditions for qPCR were validated and optimized, and a simple, efficient, and student-friendly protocol was developed. A cohort of upper-level biology students extracted DNA from pet foods and conducted the qPCR reactions. Specificity of amplification was determined by conducting melting point analysis and agarose gel electrophoresis of the products. Student reactions were analyzed and efficacy of this approach for deepening understanding of fundamental biochemical and molecular biology concepts was documented. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):536-546, 2018.
Subject(s)
Animal Feed/analysis , DNA/genetics , Food Analysis , Laboratories , Molecular Biology/education , Pets , Students , Universities , Animals , Polymerase Chain Reaction/methods , Polymerase Chain Reaction/standardsABSTRACT
BACKGROUND/AIM: Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity. MATERIALS AND METHODS: Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells. RESULTS: Rau 015 (15 µM) and curcumin (112.5 µM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 µM) and curcumin (100 µM) displayed similar effects in MCF-7 and MG-63 cells. CONCLUSION: We report on the potential of Rau 015 or Rau 018 as anti-breast cancer agents when combined with curcumin.
Subject(s)
Cell Proliferation/drug effects , Curcumin/pharmacology , Drug Screening Assays, Antitumor/methods , Naphthoquinones/pharmacology , Alkaline Phosphatase/metabolism , Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Dose-Response Relationship, Drug , Drug Synergism , Female , Humans , Insulin-Like Growth Factor Binding Protein 3/metabolism , MCF-7 Cells , Molecular Structure , Naphthoquinones/chemistry , Receptors, Estrogen/metabolismABSTRACT
BACKGROUND: Routine quantification of platelet-derived extracellular vesicles (PL-EVs) may be useful in the quality control (QC) of platelet concentrates (PCs). The aim of this multicenter study was to establish and validate a consensus protocol for the standardized PL-EV quantification using conventional flow cytometers. STUDY DESIGN AMD METHODS: Eighty-six PCs were investigated in five blood transfusion centers (A-E) on Days 0 and 5. The centers used different apheresis instruments: Trima Accel (n = 56) and/or Amicus (n = 30). PCs were prepared using standard methods (sd-PCs; n = 73; A-D) or with pathogen inactivation (PI [PI-PCs]; n = 13; E). Platelet (PLT) count was determined using conventional hematology analyzers. PLT degranulation (P-selectin expression in response to thrombin receptor PAR1 activation) and PL-EVs were analyzed by flow cytometry. RESULTS: During storage, PLT count remained stable in 58 PCs (A, C, E), whereas a decrease was observed in 12 PCs (B). PLT degranulation declined in all PCs (p < 0.001) and PL-EVs increased in 74 PCs (A, C-E; p < 0.001). Certain donor variables (e.g., plasma cholesterol, immature PLT fraction) were associated with lower PL-EVs. In Trima-produced PCs, PL-EVs were significantly lower (D) and PLT degranulation was superior compared to PCs prepared with the Amicus (A, D). PL-EVs were 10-fold lower in PI-PCs, compared to sd-PCs. However, similar QC trends were demonstrated for both PC groups during storage. CONCLUSION: PL-EV analysis in a QC program of PCs was successfully performed with results comparable among the different centers. PLT degranulation and vesiculation were primarily affected by preparation techniques.
Subject(s)
Blood Platelets/metabolism , Extracellular Vesicles/metabolism , Plateletpheresis , Female , Flow Cytometry , Humans , Male , Quality ControlSubject(s)
Humans , Psychotherapy , Combined Modality Therapy , Mental Disorders/therapy , Psychiatry/history , Psychiatry/trendsABSTRACT
O presente trabalho descreve a metodologia e os resultados do segmento de Porto Alegre, Rio Grande do Sul do Estudo Multicentrico de Morbidade Neurologica e Psiquiatrica em Areas Urbanas Brasileiras. E a primeira experiencia em nosso meio de ampla investigacao de diagnosticos psiquiatricos em populacoes urbanas. Realizada de julho de 1990 a janeiro de 1991, determinou, atraves de um instrumento de screening (QMPA), na sua primeira fase, e com IS-DSM-III na segunda fase, a prevalencia de diagnosticos psiquiatricos nesta populacao. A prevalencia estimada de morbidade psiquiatrica nessa amostra foi de 49 por cento, sendo os tres diagnosticos mais frequentes encontrados: transtornos do uso de substancias psicoativas (24,6 por cento), transtornos de ansiedade (23 por cento) e transtornos afetivos (10,7 por cento).
Subject(s)
Morbidity , Mental Disorders , Morbidity , Mental DisordersABSTRACT
O presente trabalho descreve a metodologia e os resultados do segmento de Porto Alegre, Rio Grande do Sul do Estudo Multicêntrico de Morbidade Neurológica e Psiquiátrica em Areas Urbanas Brasileiras. É a primeira experência em nosso meio de ampla investigaçäo de diagnósticos psiquiátricos em populaçöes urbanas. Realizada de julho de 1990 a janeiro de 1991, determinou através de um instrumento de screening (QMPA), na sua 1§ fase, e com IS-DSM-III na 2§ fase, a prevalência de diagnósticos psiquiátricos nesta populaçäo. A prevalência estimada de morbidade psiquiátrica nessa amostra foi de 49 por cento, sendo os três diagnósticos mais frequentemente encontrados: transtornos do uso de substâncias psicoativas (24,6 por cento), transtornos de ansiedade (23 por cento) e transtornos afetivos (10,7 por cento)
Subject(s)
Mental Disorders/epidemiology , Morbidity Surveys , Anxiety Disorders/epidemiology , Mood Disorders/epidemiology , Multicenter Studies as Topic , Psychotic Disorders/epidemiology , Urban PopulationABSTRACT
O presente trabalho descreve a metodologia e os resultados do segmento de Porto Alegre, Rio Grande do Sul do Estudo Multicêntrico de Morbidade Neurológica e Psiquiátrica em Areas Urbanas Brasileiras. É a primeira experiência em nosso meio de ampla investigaçäo de diagnósticos psiquiátricos em populaçöes urbanas. Realizada de julho de 1990 a janeiro de 1991, determinou, através de um instrumento de screening (QMPA), na sua 1ª fase, e com IS-DSM-III na 2ª fase, a prevalência de diagnósticos nesta populaçäo. A prevalência estimada de morbidade psiquiátrica nessa amostra foi de 49//, sendo os três diagnósticos mais frequentemente encontrados: transtornos do uso de substâncias psicoativas (24,6//), transtornos de ansiedade (23//) e transtornos afetivos (10,7//)
Subject(s)
Mental Disorders/epidemiology , Morbidity Surveys , Anxiety Disorders/epidemiology , Mental Health , Mood Disorders/epidemiology , Psychotic Disorders/epidemiology , Urban PopulationABSTRACT
O presente trabalho descreve a metodologia e os resultados do segmento de Porto Alegre, Rio Grande do Sul do Estudo Multicentrico de Morbidade Neurologica e Psiquiatrica em Areas Urbanas Brasileiras. E a primeira experiencia em nosso meio de ampla investigacao de diagnosticos psiquiatricos em populacoes urbanas. Realizada de julho de 1990 a janeiro de 1991, determinou, atraves de um instrumento de screen-ing (QMPA), na sua primeira fase, e com IS-DSM-III na segunda fase, a prevalencia de diagnosticos psiquiatricos nesta populacao. A prevalencia estimada de morbidade psiquiatrica nessa amostra foi de 49 por cento, sendo os tres diagnosticos mais frequentemente encontrados: transtornos do uso de substancias psicoativas (24,6 por cento), transtornos de ansiedade (23 por cento) e transtornos afetivos (10,7 por cento).
Subject(s)
Morbidity , Psychiatry , Population , Morbidity , Psychiatry , PopulationABSTRACT
O artigo apresenta alguns dados de prevalência de transtornos de ansiedade, abuso e/ou dependencia a álcoole benzodiazepínicos, procurando ressaltar que, além de serem entidades nosológicas de alta prevalência e comorbidade confirmada pela literatura e prática médica
Subject(s)
Humans , Male , Female , Alcoholism , Anti-Anxiety Agents , Anxiety Disorders , Comorbidity , Substance-Related DisordersABSTRACT
O artigo apresenta alguns dados de prevalencia de transtornos de ansiedade, abuso e/ou dependencia a alcool e benzodiazepinicos, procurando ressaltar que, alem de serem entidades nosologicas de alta prevalencia, sao tambem de apresentacao fenomenologica semelhante e comorbidade confirmada pela literatura e pratica medica.
