The relationship between reduced choroidal thickness due to high plasma asymmetrical dimethylarginine level and increased severity of diabetic retinopathy / Altos níveis de dimetil-arginina assimétrica no plasma podem aumentar a gravidade da retinopatia diabética através da redução da espessura da coroide

ABSTRACT Purpose: To evaluate the relationship between subfoveal choroidal thickness and plasma asymmetrical dimethylarginine level and the severity of diabetic retinopathy in patients with type 2 diabetes mellitus. Methods: A total of 68 cases, including 15 patients without diabetic retinopathy, 17 patients with nonproliferative diabetic retinopathy, 16 patients with type 2 diabetes mellitus and proliferative diabetic retinopathy, and 20 healthy patients (control group), were enrolled in this study. Subfoveal choroidal thickness was measured manually using the enhanced depth imaging optical coherence tomography scanning program, and plasma asymmetrical dimethylarginine level was measured using a commercial micro enzyme-linked immunosorbent assay kit. Results: The subfoveal choroidal thickness values and plasma asymmetrical dimethylarginine levels were significantly different between the four groups (p<0.001 and p<0.001). The subfoveal choroidal thickness values were significantly lower in the proliferative diabetic retinopathy group than in the other three groups (no diabetic retinopathy, nonproliferative diabetic retinopathy, and control groups; p<0.001, p=0.045, and p<0.001, respectively). The plasma asymmetrical dimethylarginine levels were significantly higher in the proliferative diabetic retinopathy group than in the other three groups (p<0.001, p<0.04, and p<0.001, respectively). In addition, a significant negative correlation was also found between plasma asymmetrical dimethylarginine level and subfoveal choroidal thickness (p<0.001, r=-0.479). Conclusion: Asymmetrical dimethylarginine is an important marker of endothelial dysfunction and endogenous endothelial nitric oxide synthase inhibitor. The severity of diabetic retinopathy was related to increased plasma asymmetrical dimethylarginine level and reduced subfoveal choroidal thickness in type 2 diabetic patients with diabetic retinopathy.

RESUMO Objetivo: Avaliar a relação da espessura subfoveal da coroide e dos níveis plasmáticos de dimetil-arginina assimétrica com a gravidade da retinopatia diabética em pacientes com diabetes mellitus tipo 2. Métodos: Foram incluídos 68 casos, compreendendo 15 pacientes sem retinopatia diabética, 17 pacientes com retinopatia diabética não proliferativa, 16 pacientes com retinopatia diabética proliferativa, e 20 casos saudáveis (grupo de controle). A espessura subfoveal da coroide foi medida manualmente, usando o programa de varredura com tomografia computadorizada óptica com imagem profunda aprimorada, e os níveis plasmáticos de dimetil-arginina assimétrica foram medidos usando um kit microELISA comercial. Resultados: Os valores da espessura subfoveal da coroide e os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente diferentes nos quatro grupos (p<0,001 para ambos os parâmetros). Os valores da espessura subfoveal da coroide foram significativamente menores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (sem retinopatia diabética, retinopatia diabética não proliferativa e grupo de controle, com p<0,001, p=0,045 e p<0,001, respectivamente). Já os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente maiores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (p<0,001, p=0,04 e p<0,001, respectivamente). Além disso, também foi encontrada uma correlação negativa significativa entre os níveis plasmáticos de dimetil-arginina assimétrica e a espessura subfoveal da coroide (p<0,001, r=-0,479). Conclusão: A dimetil-arginina assimétrica é um importante marcador de disfunção endotelial e um inibidor endógeno da óxido nítrico sintase. Foi encontrada uma relação da gravidade da retinopatia diabética e de níveis elevados de dimetil-arginina assimétrica no plasma com a redução da espessura subfoveal da coroide em pacientes diabéticos tipo 2 com retinopatia diabética.

Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery

Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Amazonian soil fungi are efficient degraders of glyphosate herbicide; novel isolates of Penicillium, Aspergillus, and Trichoderma / Os fungos do solo amazônico são degradadores eficientes do herbicida glifosato; novos isolados de Penicillium, Aspergillus e Trichoderma

Abstract Pesticide residues that contaminate the environment circulate within the hydrological cycle can accumulate within the food chain and cause problems to both environmental and human health. Microbes, however, are well known for their metabolic versatility and the ability to degrade chemically stable substances, including recalcitrant xenobiotics. The current study focused on bio-prospecting within Amazonian rainforest soils to find novel strains fungi capable of efficiently degrading the agriculturally and environmentally ubiquitous herbicide, glyphosate. Of 50 fungal strains isolated (using culture media supplemented with glyphosate as the sole carbon-substrate), the majority were Penicillium strains (60%) and the others were Aspergillus and Trichoderma strains (26 and 8%, respectively). All 50 fungal isolates could use glyphosate as a phosphorous source. Eight of these isolates grew better on glyphosate-supplemented media than on regular Czapek Dox medium. LC-MS revealed that glyphosate degradation by Penicillium 4A21 resulted in sarcosine and aminomethylphosphonic acid.

Resumo Resíduos de agrotóxicos que contaminam o meio ambiente circulam no ciclo hidrológico, podendo se acumular na cadeia alimentar e causar problemas tanto à saúde ambiental quanto humana. Por sua vez, microrganismos são bem conhecidos por sua versatilidade metabólica e capacidade de degradar substâncias quimicamente estáveis, incluindo xenobióticos recalcitrantes. O estudo atual se concentrou na bioprospecção nos solos da floresta amazônica para encontrar novas linhagens de fungos capazes de degradar com eficiência o herbicida onipresente na agricultura e no meio ambiente, o glifosato. Entre os 50 fungos isolados (usando meio de cultura suplementado com glifosato como única fonte de carbono), a maioria eram isolados do gênero Penicillium (60%) e os outros eram isolados de Aspergillus e Trichoderma (26 e 8%, respectivamente). Todos os 50 isolados de fungos foram capazes de usar glifosato como fonte de fósforo. Oito desses isolados cresceram melhor em meio suplementado com glifosato do que em meio Czapek Dox regular. LC-MS revelou que a degradação do glifosato por Penicillium 4A21 resultou nos metabólitos sarcosina e ácido aminometilfosfônico.

Normalized difference vegetation index for desiccation evaluation with glyphosate + 2, 4-D in magnetized spray solution / Índice de vegetação por diferença normalizada para avaliação de dessecação com glyphosate + 2, 4-D em calda magnetizada

Abstract Water magnetization and geoprocessing are increasingly utilized tools in weed management. Our objective was to study the influence of water magnetization on herbicide efficiency and to verify whether there is a relationship between control scores and the normalized difference vegetation index (NDVI). In the laboratory experiment, water was subjected to magnetization and evaluated with respect to four characteristics. In the field experiment, plots of Brachiaria grass were subjected to treatments in a factorial scheme (6 × 2 + 1). Six herbicidal factors (doses of glyphosate and glyphosate + 2,4-D) and the magnetization or absence of magnetization of the spray solution were evaluated and compared against the control treatment (without spraying). Weed control assessments were carried out six times. Images were obtained using an embedded multispectral camera to determine the NDVI values. Data related to water characteristics were analyzed using the t test. Weed control and NDVI data were subjected to analysis of variance and are presented in regression graphs. Dispersion analysis of NDVI data was performed according to the control scores. The magnetization process decreased the pH of the water and increased the surface tension, but it did not influence the control scores or the NDVI. As the glyphosate dose was increased, the control scores were higher and the NDVI values were lower. Magnetized water did not affect the biological efficiency of the herbicides, and there was a strong correlation between the control scores and the NDVI values.

Resumo A magnetização da água e o geoprocessamento são ferramentas cada vez mais utilizadas no manejo de ervas daninhas. Nosso objetivo foi estudar a influência da magnetização da água na eficiência do herbicida e verificar se existe uma relação entre os escores de controle e o índice de vegetação por diferença normalizada (NDVI). No experimento de laboratório, a água foi submetida à magnetização e avaliada em relação a quatro características. No experimento de campo, parcelas de capim-braquiária foram submetidas a tratamentos em esquema fatorial (6 × 2 + 1). Seis fatores herbicidas (doses de glyphosate e glyphosate + 2,4-D) e a magnetização ou ausência de magnetização da calda foram avaliados e comparados com o tratamento controle (sem pulverização). Avaliações de controle de plantas daninhas foram realizadas seis vezes. As imagens foram obtidas usando uma câmera multiespectral incorporada para determinar os valores de NDVI. Os dados relacionados às características da água foram analisados ​​por meio do teste t. O controle de plantas daninhas e os dados de NDVI foram submetidos à análise de variância e são apresentados em gráficos de regressão. A análise de dispersão dos dados NDVI foi realizada de acordo com os escores de controle. O processo de magnetização diminuiu o pH da água e aumentou a tensão superficial, mas não influenciou nos escores de controle ou no NDVI. Conforme a dose de glyphosate foi aumentada, os escores de controle foram maiores e os valores de NDVI foram menores. A água magnetizada não afetou a eficiência biológica dos herbicidas, e houve uma forte correlação entre os escores de controle e os valores de NDVI.

Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer / Aumento da anexina V em resposta à combinação de galato de epigalocatequina e quercetina como uma potente parada do ciclo celular do câncer colorretal

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.

Evaluación de la prueba Aspergillus Galactomannan Ag VircliaR Monotest como alternativa a kit Platelia ™ Aspergillus EIA / Evaluation of the Aspergillus Galactomannan ag VircliaR Monotest test as an alternative to Platelia™ Aspergillus EIA kit

INTRODUCCIÓN: La prueba Aspergillus galactomannan Ag Virclia® (GM-VClia) es una técnica de galactomanano monotest, auto-matizada, basada en inmunoensayo quimioluminiscente (CLIA). OBJETIVO: Evaluar el desempeño del test de GM-VClia en muestras de suero y lavado bronquioalveolar (LBA) procesadas previamente con el kit Platelia™ Aspergillus EIA (GM-Plat). MATERIALES Y MÉTODOS: Se estudiaron 56 muestras de suero y 40 de LBA, correspondientes a un total de 59 pacientes (algunos con determinación de galactomamano en ambas muestras) con enfermedades pulmonares, hematológicas, LES, Covid-19 y tumores, entre otros. Trece pacientes tuvieron aspergilosis invasora (1 probada y 12 probables). RESULTADOS: La correlación entre ambos métodos para suero y LBA fue r = 0,8861 p < 0,0001 y r = 0,6368 p < 0,001, respectivamente. Hubo una concordancia global de 67,7% (65/96), siendo de 85,7% (48/56) en sueros y 42,5,0% (14/49) en LBA. Al subir el punto de corte en LBA por GM-VClia la concordancia aumentó a 85,7%. CONCLUSIONES: Se observó una mayor correlación y concordancia en sueros que en LBA. El kit GM-VClia presentó una mayor sensibilidad y valor predictor negativo (VPN), que el kit GM-Plat. Las desventajas de GM-VClia, la constituyen la categoría "dudoso", que dificulta la interpretación y que, con los puntos de corte actuales en LBA, la correlación con GM-Plat es menor. Las ventajas son su mayor sensibilidad, facilidad de procesamiento y una mayor rapidez en los resultados.

BACKGROUND: The Aspergillus Galactomannan Ag Virclia® (GMVClia) test is a monotest and automated galactomannan technique based on chemiluminescent immunoassay (CLIA). AIM: To evaluate the performance of the GM-VClia test in serum and bronchioalveolar lavage (BAL) samples previously processed with the Platelia ™ Aspergillus EIA kit (GM-Plat). METHODS: 56 samples of serum 40 from BAL (some of them with galactomaman determination in both samples), from patients with pulmonary diseases, hematological diseases, SLE, Covid-19 and tumors, among others, were studied. Thirteen patients had invasive aspergillosis (1 proven and 12 probable). RESULTS: The correlation between both methods for serum and BAL was r = 0.8861 p < 0.0001 and r = 0.6368 p < 0.001, respectively. There was a global concordance of 67.7% (65/96), being 85.7% (48/56) in sera and 42.5.0% (14/49) in BAL. By raising the cut-off point in LBA by GM-VClia, the agreement increased to 85.7%. CONCLUSION: A greater correlation and concordance was observed in sera than in BAL. The GM-VClia kit had a higher sensitivity and NPV than the GM-Plat kit. The disadvantages of GM-VClia are the "doubtful" category, which makes interpretation difficult and that with the current cut-off points in LBA the correlation with GM-Plat is lower. The advantages are its greater sensitivity, ease of processing and faster results.

Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

Tratamiento con análogos de la hormona liberadora de gonadotrofinas (aGnRH) en niñas, niños y adolescentes / Treatment with gonadotropin-releasing hormone analogs (GnRHa) in childhood and adolescence

Desde hace varias décadas, los análogos de la hormona liberadora de gonadotrofinas (aGnRH) son el tratamiento de elección en la pubertad precoz central (PPC) en niñas y en niños. Causan una inhibición del eje hipotálamo-hipófiso-gonadal, disminuyen la secreción de gonadotrofinas, estradiol y testosterona; como consecuencia, producen una regresión de los caracteres sexuales secundarios durante el tratamiento. En los últimos años, estos análogos también se utilizan en adolescentes transgénero, en adolescentes y adultas jóvenes con enfermedades oncológicas, en algunas situaciones muy particulares en niños y niñas con talla baja, y en pacientes con trastornos del neurodesarrollo. En Argentina, los más utilizados son el acetato de triptorelina y el acetato de leuprolide en sus formas de depósito. Estos medicamentos han demostrado eficacia y seguridad. El objetivo de esta publicación es realizar una revisión y actualización del uso de los aGnRH en niños, niñas y adolescentes.

For several decades, gonadotropin releasing hormone analogs (GnRHa) are the medical treatment selected for central precocious puberty (CPP) in girls and boys. They generate an inhibition of the hypothalamus-pituitarygonadal axis decreasing LH, FSH, estradiol and testosterone secretion and, in this way, they produce a regression of secondary sexual characters under treatment. In the last years, these analogs are also used in trans adolescents, in adolescents and young adults with oncological diseases, in some very particular situations in children with short stature and in patients with neurodevelopmental disorders. In Argentina the most commonly used formulations are triptorelin and leuprolide acetate depot forms. These analogs have proven both their efficacy and their safety. The aim of this paper is to review and update about the use of GnRHa in children and adolescents.

Eficacia y seguridad de Molnupiravir para el tratamiento de COVID-19: actualización enero 2022 / Eficacia y seguridad de Molnupiravir para el tratamiento de COVID-19: nueva actualización 2022

INTRODUCCIÓN: El virus SARS-CoV-2, sigue presentando múltiples variantes, el espectro de la enfermedad es amplio e incluye desde cuadros leves y autolimitados hasta neumonía atípica severa y progresiva, falla multiorgánica y muerte. Actualmente, existen vacunas eficaces para prevenir COVID-19, y se están desarrollando otras más nuevas para la prevención del COVID-19 grave, asimismo algunos medicamentos muestran resultados promisorios para prevenir y combatir esta enfermedad. Sin embargo, se carece de fármacos antivirales eficaces para combatir esta enfermedad. Aunque algunos de los medicamentos han recibido recientemente una autorización de uso de emergencia (EUA) para COVID-19, todos estos agentes farmacéuticos deben administrarse en entornos hospitalarios. Este documento fue elaborado para actualizar la evidencia científica disponible respecto a la eficacia y seguridad de Molnupiravir en el tratamiento de COVID-19. OBJETIVO: El objetivo de este documento es actualizar la evidencia científica disponible respecto a la eficacia y seguridad de Molnupiravir en el tratamiento de COVID-19, mejorando los desenlaces de los pacientes, y/o previniendo la enfermedad COVID-19 causada por el virus SARS-CoV-2. MÉTODOS: En la SNT N° 08-2021: E

Antifungal activity of silver nanoparticles and clotrimazole against Candida spp

Abstract The aim of present study was calculate the Minimum inhibitory concentrations (MICs) of silver nanoparticles and clotrimazole for Candida species and their interaction by the adaptation of standarized methods. The MICs values of clotrimazole were 9 E-04-3 E-03 ug/ml, 0.1-0.6 ug/ml, 3 E-03- 0.1 ug/ml and 3 E-03-0.3 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. The MICs values of silver nanoparticles were 26.50- 53 ug/ml; 26.50-106 ug/ml; 106-212 ug/ ml and 26.50- 53 ug/ml for Candida albicans susceptible to fluconazole, Candida albicans resistance to fluconazole, Candida krusei and Candida parapsilosis respectively. Synergism between clotrimazole and silver nanoparticles was measured by checkerboard BMD (broth microdilution) test and shown only for C. albicans susceptible to fluconazole because the fractional inhibitory concentrations (FICs) values were 0.07 - 0.15 ug/ml. Indifference was shown for the other species tested because the FICs values were between 0.5 - 2- 3.06 ug/ml. The results suggest synergistic activity depending on the fungus species analysed, however we recommend the incorporation of others measurement methodologies to confirm our results. As for measurement methodologies of MICs of silver nanoparticles and clotrimazole international normative were respected to guarantee reproducible and comparable results.

Desirability Function in analytical method development for determination of glitazones and metabolites employing HF-LPME

Abstract Thiazolidinedione, often shortened to TZD or glitazone, helps lower insulin resistance, which is the underlying problem for many people with type 2 diabetes. The two most known glitazones are pioglitazone (PGZ), with the brand name medicine Actos®, and rosiglitazone (RSG), which is Avandia®. This study presented a multivariate optimization in the microextraction procedure employing Fractional Factorial Design (FFD) combined with Desirability Function (DF) to determine TZD and metabolites in biological samples. Microextraction requires several parameters to be optimized; however, most of them still use univariate optimization. Finding optimum conditions by simple response is relatively simple, but the problems, in case of microextractions, are often more complex when it has more responses. For example, changing one factor that promotes one response may suppress the effect of the others. Thus, this multivariate optimization was applied for two bioanalytical methods for determination of TZD and metabolites, one by HPLC and other by CE, both using Hollow Fiber Liquid-Phase Microextraction (HF-LPME). The results establish the optimal values and elucidate how the factors that affect HF-LPME procedure perform in extraction efficiency for TZDs. Additionally, this study demonstrates that DF can be an important tool to optimize microextraction procedures.

Polystyrene-b-poly (acrylic acid) nanovesicles coated by modified chitosans for encapsulation of minoxidil

Abstract In this work, polystyrene-b-poly (acrylic acid) (PS-b-PAA) nanovesicles were coated by modified chitosans aiming at studying its physicochemical parameters. The chitosan (CS) was chemically modified to add hydrophilic and/or hydrophobic groups, obtaining three modified chitosans. The PS-b-PAA nanovesicles were obtained by organic (1,4-dioxane) cosolvent method in water, resulting in nanovesicles with less than 150 nm of diameter (polydispersibility index - PDI at 90° = 0.106), measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and negative zeta potential (-37.5 ± 3.2 mV), allowing the coating of its surface with oppositely charged polysaccharides, such as the CS and the modified chitosans. The coating process was made by mixing the colloidal suspensions with the CS and the modified chitosans at specific ENT#091;CS-xENT#093;/ENT#091;PS-b-PAAENT#093; ratios (0.001 to 1.0 wt %) and measuring the change in size and surface charge by DLS and zeta potential. Upon reaching maximum adsorption, the zeta potential parameter was positively stabilized (+26.7 ± 4.1 mV) with a hydrodynamic diameter slightly longer (< 200 nm of diameter). The encapsulation efficiency (EE) of minoxidil, quantified by capillary electrophoresis, was 50.7%, confirming their potential as drug delivery carriers and the coating process showed the possibility of controlling the surface charge nature of these nanovesicles

Research on Molecular Mechanism of Fructus Ligustri Lucidi against Osteoporosis based on Network Pharmacology

Abstract TCMSP platform of systematic pharmacology of traditional Chinese medicine This study aimed to investigate the molecular mechanism of Fructus Ligustri Lucidi (NZZ, Chinese abbreviation) against osteoporosis (OP) by means of network pharmacology.ChemDraw Professional 15.1 software and Molinspiration Smiles database were used to draw the chemical formulas of the components. The active ingredients and related target proteins of NZZ were searched in platform of systematic pharmacology of traditional Chinese medicine database, Drugbank, Therapeutic Target Database, SymMap and other databases. Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the selected target through Enrichr and KEGG Automatic Annotation databases, and their mechanism was studied. A total of 29 compounds and 140 corresponding targets, including 14 key targets and 14 protein factors in protein-protein interaction core network were obtained. The key targets were tumor necrosis factor(TNF), interleukin(IL)-6R and sestrogen receptor alpha. The number of GO items was 466 (P<0.05), including 399 items of biological process (BP), 54 items of cell composition (MF) and 13 items of molecular function (CC). KEGG pathway enrichment screened 85 signaling pathways (P<0.05), including the IL-17 signaling pathway, TNF signaling pathway, advanced glycation end products and their receptors signaling pathway and cAMP signaling pathway. The active ingredients of NZZ. exert their anti-OP effects through multi-components, multi-targets and multi-pathways, which can provide new evidence for further study of their anti-OP mechanism.

Optimization of glycerol-based medium composition for antifungal metabolites production by Bacillus subtilis

Abstract Bacillus species are promising producers of various compounds that have pronounced antimicrobial, antiviral and antitumor activities. Due to its GRAS status, Bacillus subtilis represents an excellent candidate for the usage in plant pathogens biocontrol. In this research, evaluation of antifungal metabolites biosynthesis by Bacillus subtilis ATCC 6633 and optimization of glycerol-based medium composition, using response surface methodology, for the production of compounds effective against Neurospora crassa were investigated. The results of disc-diffusion method indicate that applied Bacillus strain produces compounds with antifungal activity against tested fungus. In order to find optimal cultivation medium composition, the experiments were carried out in accordance with Box-Behnken design, and optimization was performed using the concept of desirability function combined with previously defined mathematical equation, which describes examined bioprocess. The optimization model predicts that maximum inhibition zone diameter against Neurospora crassa of 32.24 mm is achieved when initial content of glycerol, NaNO2 and K2HPO4 were 49.68 g/L, 2.90 g/L and 6.49 g/L, respectively. Additionally, the second optimization set was made to minimize the consumption of medium components and costs of medium preparation. The obtained results are the basis for further research aimed to develop medium appropriate for economically justified production of bioactive compounds at industrial scale.

In vitro cytotoxicity assay of Fucoidan extracted from Turbinaria conoides against cancer cell lines MCF7, A549, and normal cell line L929

Abstract The main aim of the study is to quantify the cytotoxic property of the Fucoidan extracted from the Turbinaria conoides using the MTT assay with the standard fucose. Fucoidan was extracted using the soaked water method and it was determined using the HPLC procedure the obtained Test sample Fucoidan extracted from the Turbinaria conoides and standard fucose was subjected to the cytotoxicity assay against the MCF7 Human breast cancer cell line, A549 lung cancer cell line, and L929 normal mouse fibroblast cell line. From the results it was found that the Test sample showed good IC50 value for MCF7 cell line then A549 with an increasing concentration 24 hours incubation at 37°C The IC50 for MCF7 was 115.21 µg/ml and A549 396.46µg/ml and the Fucoidan extract was checked for its cytotoxicity against the normal mouse fibroblast cell line L929, Fucoidan was found non-lethal to the L929 mouse fibroblast normal cell line. Standard fucose also gave a significant result towards MCF7 and against the L929. This indicates that the Fucoidan extracted from Tubinaria conoides shows better anticancer potential in it. Hence its application can be further extended in the pharmacological fields.

Genetic, sociodemographic and lifestyle factors associated with serum 25-hydroxyvitamin D concentrations in Brazilian adults: the Pró-Saúde Study / Fatores genéticos, sociodemográficos e de estilo de vida nas concentrações séricas de 25-hidroxivitamina D em adultos brasileiros: o Estudo Pró-Saúde / Factores genéticos, sociodemográficos y estilo de vida asociados con la concentración sérica 25-hidroxivitamina D en adultos brasileños: Estudio Pro-Salud

This study aims to investigate factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentration in Brazilian adults considering sociodemographic and lifestyle factors, as well as vitamin D-related single nucleotide polymorphisms (SNPs). This is a cross-sectional study (n = 491; 34-79y; 251 women), nested within a prospective cohort (Pró-Saúde Study). Associations between serum 25(OH)D and sociodemographic characteristics, diet, use of supplement, physical activity, season of blood collection, body fat, skin type, sun exposure index, and SNPs CYP2R1-rs10741657 and GC-rs2282679 were explored by multiple linear regression. The prevalence of serum 25(OH)D < 50nmol/L was 55%. Serum 25(OH)D was lower among women (β = -4.38; 95%CI: -8.02; -0.74), those with higher visceral fat (β = -4.02; 95%CI: -5.92; -2.12), and those with AC and CC genotypes for GC-rs2282679 (β = -6.84; 95%CI: -10.09; -3.59; β = -10.63; 95%CI: -17.52; -3.74, respectively). Factors directly associated with serum 25(OH)D included summer (β = 20.14; 95%CI: 14.38; 25.90), intermediate skin type (β = 6.16; 95%CI: 2.52; 9.80), higher sun exposure (β = 0.49; 95%CI: 0.22; 0.75), vitamin D intake (β = 0.48; 95%CI: 0.03; 0.93), and physical activity (β = 4.65; 95%CI: 1.54; 7.76). Besides physical activity, diet, and sun exposure, non-modifiable factors, such as GC genotypes must be considered when evaluating vitamin D insufficiency in mixed-race populations. Moreover, high visceral fat in association with poorer vitamin D status deserve attention given that both conditions are unfavorably related with chronic and acute health outcomes.

Este estudo teve como objetivo investigar fatores associados com as concentrações séricas de 25-hidroxivitamina [25(OH)D] em adultos brasileiros de acordo com fatores sociodemográficos e de estilo de vida, assim como de polimorfismos de nucleotídeo único (SNPs) relacionados à vitamina D. Este é um estudo transversal (n = 491; 34-79 anos; 251 mulheres) aninhado em uma coorte prospectiva (Estudo Pró-Saúde). Associações entre a 25(OH)D sérica e características sociodemográficas, consumo alimentar, uso de suplementos, atividade física, estação do ano na coleta da amostra de sangue, gordura corporal, fototipo de pele, índice de exposição solar e SNPs CYP2R1-rs10741657 e GC-rs2282679, explorados por regressão multilinear. A prevalência de 25(OH)D sérica < 50nmol/L foi 55%. A concentração sérica de 25(OH)D foi menor entre mulheres (β = -4,38; IC95%: -8,02; -0,74), indivíduos com mais gordura visceral (β = -4,02; IC95%: -5,92; -2,12) e genótipos AC e CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 e β = -10,63; IC95%: -17,52; -3,74, respectivamente). Os fatores associados diretamente à 25(OH)D sérica incluíram os meses de verão (β = 20,14; IC95%: 14,38; 25,90), fototipo intermediário (β = 6,16; IC95%: 2,52; 9,80), maior exposição solar (β = 0,49; IC95%: 0,22; 0,75), ingestão de vitamina D (β = 0,48; IC95%: 0,03; 0,93) e atividade física (β = 4,65; IC95%: 1,54; 7,76). Além de atividade física, dieta e exposição solar, fatores não modificáveis, tais como variantes do gene GC devem ser considerados na avaliação da deficiência de vitamina D em populações miscigenadas. Além disso, merece atenção a associação entre a gordura visceral elevada e o pior estado de vitamina D, uma vez que ambas as condições implicam em desfechos de saúde desfavoráveis, tanto crônicos quanto agudos.

Nuestro objetivo fue investigar factores asociados con la concentración sérica 25-hidroxivitamina D [25(OH)D] en adultos brasileños, considerando factores sociodemográficos y de vida, así como también los polimorfismos de nucleótido único relacionados con la vitamina D (SNPs). Se trata de un estudio transversal (n = 491; 34-79 años; 251 mujeres), anidado dentro de una cohorte prospectiva (Estudio Pro-Salud). Se investigaron las asociaciones entre concentración sérica 25(OH)D y características sociodemográficas, ingesta alimentaria, uso de suplementos, actividad física, estación del año de recogida de muestras de sangre, grasa corporal, tipo de piel, índice de exposición al sol, y SNPs CYP2R1-rs10741657 y GC-rs2282679 mediante una regresión múltiple lineal. La prevalencia sérica 25(OH)D < 50nmol/L fue 55%. La 25(OH)D sérica fue menor entre las mujeres (β = -4,38; IC95%: -8,02; -0,74), quienes tenían alta grasa visceral (β = -4,02; IC95%: -5,92; -2,12), genotipos AC y CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 y β = -10,63; IC95%: -17,52; -3,74, respectivamente). Los factores directamente asociados con la concentración sérica 25(OH)D incluyeron verano (β = 20,14; IC95%: 14,38; 25,90), tipo de piel intermedia (β = 6,16; IC95%: 2,52; 9,80), más alta exposición al sol (β = 0,49; IC95%: 0,22; 0,75), toma de vitamina D (β = 0,48; IC95%: 0,03; 0,93) y actividad física (β = 4,65; IC95%: 1,54; 7,76). Además de la actividad física, dieta y exposición al sol, los factores no modificables, tales como genotipos GC, necesitan tenerse en cuenta cuando se está evaluando la insuficiencia de vitamina D en poblaciones mestizas. Asimismo, las implicaciones de la asociación de una alta grasa visceral con un estatus más pobre de vitamina D merece que se le preste atención, puesto que ambas condiciones de salud están relacionadas desfavorablemente con resultados de salud graves y crónicos.