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Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.
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Fotoquimioterapia , Fármacos Fotossensibilizantes , Rosa Bengala , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Rosa Bengala/química , Rosa Bengala/farmacologia , Rosa Bengala/uso terapêutico , Linhagem Celular Tumoral , Humanos , Oxigênio Singlete/metabolismo , Parvovirus B19 Humano/efeitos dos fármacos , Parvovirus B19 Humano/química , Neoplasias/tratamento farmacológico , Luciferases de Vaga-Lume/metabolismo , FemininoRESUMO
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.
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In current systems, the fermentation spontaneous process produces fermented beans of heterogeneous quality due to the fermentation time. This study demonstrated that the fermentation time should be reduced. For this purpose, the physicochemical parameters, antioxidant profile, and volatile compounds were characterized in two types of fermentation (spontaneous and starter culture) for 168 h in cocoa from three altitude levels. Multivariate analysis (cluster and PCA) was used to discriminate the fermentation stages. We found three stages in all fermentations, where the first two stages (0 h to 96 h) were characterized by a higher antioxidant potential of the cocoa bean and the presence of desirable volatile compounds such as acids, alcohols, aldehydes, ketones, and esters, which are precursors of cocoa aroma; however, prolonged fermentation times affected the antioxidant profile of the bean. In addition, the use of a starter culture facilitates the release of compounds in a shorter time (especially alcohols and esters). It is concluded that it is necessary to reduce the fermentation time under these conditions in the region of Amazonas.
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Mexico City is the location with the largest number of boxers in Mexico; in fact, it is the first city in the country to open a Technological Baccalaureate in Education and Sports Promotion with a pugilism orientation. This cross-sectional study aimed to determine the physical-functional profile of applicants for admission to the baccalaureate in sports. A total of 227 young athletes (44F; 183M; 15.65 (1.79) years; 63.66 (14.98) kg; >3 years of boxing experience) participated in this study. Body mass (BM), maximal isometric handgrip (HG) strength, the height of the countermovement jump (CMJ), the velocity of straight boxing punches (PV), and the rear hand punch impact force (PIF) were measured. The young boxers were profiled using unsupervised machine learning algorithms, and the probability of superiority (ρ) was calculated as the effect size of the differences. K-Medoids clustering resulted in two sex-independent significantly different groups: Profile 1 (n = 118) and Profile 2 (n = 109). Except for BM, Profile 2 was statistically higher (p < 0.001) with a clear distinction in terms of superiority on PIF (ρ = 0.118), the PIF-to-BM ratio (ρ = 0.017), the PIF-to-HG ratio (ρ = 0.079) and the PIF-to-BM+HG ratio (ρ = 0.008). In general, strength levels explained most of the data variation; therefore, it is reasonable to recommend the implementation of tests aimed at assessing the levels of isometric and applied strength in boxing gestures. The identification of these physical-functional profiles might help to differentiate training programs during sports specialization of young boxing athletes.
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BACKGROUND: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. METHODS: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). RESULTS: At baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72-98%), and 66% (95% CI: 48-90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. CONCLUSION: Our study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/epidemiologia , Hipertensão Arterial Pulmonar/terapia , América Latina/epidemiologia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/terapia , Estudos Retrospectivos , Hipertensão Pulmonar Primária Familiar , Medição de Risco , PrognósticoRESUMO
El riesgo suicida es definido como la posibilidad de que una persona atente deliberadamente contra su vida y se considera una conducta autodestructiva de causas multifactoriales. El propósito de esta investigación fue determinar los factores psicológicos aso-ciados al riesgo suicida en estudiantes universitarios. Esto se realizó por medio de un enfoque cuantitativo no experimental. La muestra estuvo conformada por 1696 estudiantes de pregrado, 54.7 % correspondiente al sexo femenino y 43.6 % al masculino. Se aplicaron escalas para evaluar sentido de la vida, depresión, esperanza, soledad, apoyo interpersonal y riesgo suicida. Los resultados indicaron que el 50 % de la muestra reportó nunca haber tenido pensamientos suicidas. Sin embargo, el 26.8 % tuvo un pensamiento pasajero al respecto; el 9.9 % planeó quitarse la vida, pero no lo intentó; el 5.8 % realizó un intento suicida sin intención real de concretar el acto, el 5 % hizo planes para quitarse la vida con intención real de concretar el acto; y el 2.4 % efectuó intentos suicidas con deseos de morir. Se evidenció que existe una relación inversa significativa entre el riesgo suicida y la esperanza, presencia y búsqueda de sentido de la vida y apoyo interpersonal. No obstante, los individuos con mayor riesgo suicida poseen puntajes más altos en soledad y depresión. Estos resultados se discuten desde sus implicaciones en el ejercicio clínico
Suicide risk is defined as the possibility of a person deliberately taking his/her own life; this is considered a self-destructive behavior with multifactorial causes. This research aimed to determine the psychological fac-tors associated with suicide risk in university students. This was done through a quantitative, non-experimental approach. The sample consisted of 1.696 undergraduate students, 54.7 % female and 43.6 % male students. Ques-tionnaires were applied to evaluate meaning in life, depression, hope, loneliness, interpersonal support, and suicide risk. The results indicated that 50 % of the parti-cipants reported never having suicidal thoughts. However, 26.8 % had had a passing thought about committing suicide, 9.9 % had thought of a specific (but unexecuted) plan to commit suicide, 5.8 % reported a previous suicide attempt without the intention of actually committing suicide, 5 % had made plans to take their own life with a real intention to commit the act, and 2.4 % had made at least one suicide attempt with a desire to die. Results indicate that there is a significant inverse relation be-tween suicide risk and hope, the presence and search for a meaning in life, and interpersonal support. However, a higher suicide risk is positively correlated with loneliness and depression. These results are discussed according to their implications in clinical practice
O risco de suicídio é definido como a possibilidade de uma pessoa deliberadamente atentar contra sua vida, considerando-o como um comportamento autodestrutivo com causas multifatoriais. O objetivo desta pesquisa foi determinar os fatores psicológicos associados ao risco de suicídio em estudantes universitários. Isso foi feito por meio de uma abordagem quantitativa, não experimental. A amostra foi composta por 1696 alunos de graduação, sendo 54.7 % do sexo feminino e 43.6 % do sexo mascu-lino. Foram aplicadas escalas para avaliar o sentido de vida, depressão, esperança, solidão, apoio interpessoal e risco de suicídio. Os resultados indicaram que 50 % da amostra relatou nunca ter tido pensamentos suicidas. No entanto, 26.8 % tiveram um pensamento passageiro sobre isso, 9.9 % planejaram se matar, mas não tentaram; 5.8 % fizeram uma tentativa de suicídio sem real intenção de realizar o ato, 5 % fizeram planos para tirar a própria vida com real intenção de realizar o ato e 2.4 % fizeram ten-tativas de suicídio com desejo de morrer. Evidenciou-se que existe uma relação inversa significativa entre risco de suicídio e esperança, presença e busca de sentido na vida e apoio interpessoal. No entanto, indivíduos com maior risco de suicídio apresentam pontuações mais altas em solidão e depressão. Esses resultados são discutidos a partir de suas implicações na prática clínica
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Humanos , Suicídio , Estudantes , Saúde Mental , Fatores de Risco , Depressão , Sistemas de Apoio Psicossocial , HondurasRESUMO
Sol-Gel is a low cost, well-established and flexible synthetic route to produce a wide range of micro- and nanostructures. Small variations in pH, temperature, precursors, time, pressure, atmosphere, among others, can lead to a wide family of compounds that share the same molecular structures. In this work, we present a general review of the synthesis of LaMnO3, SrTiO3, BaTiO3 perovskites and zinc vanadium oxides nanostructures based on Sol-Gel method. We discuss how small changes in the parameters of the synthesis can modify the morphology, shape, size, homogeneity, aggregation, among others, of the products. We also discuss the different precursors, solvents, working temperature, reaction times used throughout the synthesis. In the last section, we present novel uses of Sol-Gel with organic materials with emphasis on carbon-based compounds. All with a perspective to improve the method for future applications in different technological fields.
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Alzheimer's disease (AD) is a neurodegenerative disorder whose prevalence has an incidence in senior citizens. Unfortunately, current pharmacotherapy only offers symptom relief for patients with side effects such as bradycardia, nausea, and vomiting. Therefore, there is a present need to provide other therapeutic alternatives for treatments for these disorders. The 5-HT4 receptor is an attractive therapeutic target since it has a potential role in central and peripheral nervous system disorders such as AD, irritable bowel syndrome, and gastroparesis. Quantitative structure-activity relationship analysis of a series of 62 active compounds in the 5-HT4 receptor was carried out in the present work. The structure-activity relationship was estimated using three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques based on these structures' field molecular (force and Gaussian field). The best force-field QSAR models achieve a value for the coefficient of determination of the training set of R2training = 0.821, and for the test set R2test = 0.667, while for Gaussian-field QSAR the training and the test were R2training = 0.898 and R2test = 0.695, respectively. The obtained results were validated using a coefficient of correlation of the leave-one-out cross-validation of Q2LOO = 0.804 and Q2LOO = 0.886 for force- and Gaussian-field QSAR, respectively. Based on these results, novel 5-HT4 partial agonists with potential biological activity (pEC50 8.209-9.417 for force-field QSAR and 9.111-9.856 for Gaussian-field QSAR) were designed. In addition, for the new analogues, their absorption, distribution, metabolism, excretion, and toxicity properties were also analyzed. The results show that these new derivatives also have reasonable pharmacokinetics and drug-like properties. Our findings suggest novel routes for the design and development of new 5-HT4 partial agonists.
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Relação Quantitativa Estrutura-Atividade , Receptores 5-HT4 de Serotonina/efeitos dos fármacos , Receptores 5-HT4 de Serotonina/metabolismo , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Agonistas do Receptor 5-HT4 de Serotonina/química , Antagonistas do Receptor 5-HT4 de Serotonina/química , Relação Estrutura-AtividadeRESUMO
Introducción: la rosácea es una enfermedad inflamatoria crónica de etiología desconocida que se presenta con eritema centro facial permanente, con episodios transitorios de intensificación asociados a factores desencadenantes unido a otros síntomas y signos variados. Tiene diferentes formas clínicas, es de difícil manejo y por ello, aunque existen diferentes tratamientos, aún es válido continuar la búsqueda de otras alternativas terapéuticas. Objetivo: determinar eficacia del metronidazol gel 0.75%, permetrina crema 5%, y la combinación de ambos medicamentos en pacientes con rosácea facial tratados en el Hospital Fajardo en el período 2016 a 2017. Método: se realizó un estudio de intervención cuasi-experimental, abierto, longitudinal, aleatorizado con tres grupos de 30 pacientes, que recibieron tratamiento durante 3 meses, y fueron evaluados un mes después de terminar el tratamiento. Resultados: predominaron las mujeres, el fototipo cutáneo III, con piel grasa. La mejor respuesta terapéutica fue la asociación de ambos medicamentos con un 100% con respuesta satisfactoria, seguida de 92.9% con la permetrina y 79.3% con el metronidazol. Conclusiones: La respuesta terapéutica en la mayoría de los 3 grupos fue satisfactoria, aunque predominó la combinación de ambos medicamentos. Las reacciones adversas fueron leves y escasas.
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Humanos , Feminino , Adolescente , Adulto , Rosácea , Permetrina , Metronidazol , Preparações FarmacêuticasRESUMO
Triple-negative breast cancer is a major health problem that lacks molecular targets for therapy. Neoepitopes represent a viable option to induce antitumor immune responses, but they have limitations, such as low immunogenicity and tolerance induction. Parvovirus B19 virus-like particles may be used to deliver neoepitopes to prime cellular immunity. We designed and evaluated the therapeutic effect of VP2 B19-virus-like particles, with multi-neoepitopes, in a 4T1 breast cancer model. Balb/c mice received four therapeutic immunizations with multi-neoepitopes-virus-like, wild type-virus-like, vehicle, or virus-like plus Cry1Ac adjuvant particles, intraperitoneally and peritumorally. Tumor growth, lung macro-metastasis, and specific immune responses were evaluated. Therapeutic administration of multi-epitopes virus-like particles significantly delayed tumor growth and decreased the lung macro-metastasis number, in comparison to treatment with wild type-virus-like particles, which surprisingly also elicited antitumoral effects that were improved with the adjuvant. Only treatments with multi-epitope virus-like particles induced specific proliferative responses of CD8 and CD4 T lymphocytes and Granzyme-B production in lymphatic nodes local to the tumor. Treatment with recombinant multiple neoepitopes-virus-like particles induced specific cellular responses, inhibited tumor growth and macro-metastasis, thus B19-virus-like particles may function as an effective delivery system for neoepitopes for personalized immunotherapy.