Biomasa residual de industria del Cannabis, una alternativa para la obtención de productos de alto valor agregado

A medida que como sociedad vamos dando más importancia a lograr una economía circular, se hace importante encontrar fuentes renovables aptas para la producción de biocombustibles y bioquímicos. En los últimos años, diversas fuentes de biomasa lignocelulósica han sido estudiadas para estos propósitos. Dentro de estas fuentes de biomasa se encuentra el cáñamo (Cannabis sativa L.), siendo parte de una industria que ha crecido a pasos agigantados en las últimas décadas, en Colombia, desde su legalización. Específicamente, la industria del cannabis medicinal es responsable de generar una enorme cantidad de residuos en forma de los tallos de la planta, considerados un subproducto de bajo valor. En esta revisión se compila la información de diferentes estudios sobre el aprovechamiento de la fracción de polisacáridos de biomasa cáñamo, mediante transformaciones químicas y bioquímicas, para la obtención de productos de valor agregado. Se encontró que la mayoría de estudios están enfocados en la obtención de bioetanol o biogás; se encontraron también reportes de otras moléculas como ácido succínico, ácido láctico, furfural, polihidroxialcanoatos y bisaboleno. La viabilidad a nivel industrial de todos estos procesos permanece siendo una incógnita, pues los pasos de pretratamiento, hidrólisis y de conversión final utilizados suelen ser costosos. Es necesario que los estudios que realicen en el futuro se enfoquen en optimizar las condiciones de estos procesos y hacerlos verdes y así asegurar que puedan ser escalados.

As we as a society, give more importance to achieving a circular economy, it becomes important to find renewable sources suitable for the production of biofuels and biochemicals. In the last years, several different sources of lignocellulosic biomass have been studied for these purposes. One of these biomass sources is hemp (Cannabis sativa L), being part of an industry that has grown through giant steps in the last decades, in Colombia, since its legalization. Specifically, the industry of medicinal hemp is responsible for the generation of huge amounts of residues in the form of the plant stalks, considered a low value subproduct. This review compiles the information of several studies about the exploitation of the polysaccharide portion of hemp biomass through chemical and biochemical transformations, obtaining value-added products. It was found that most of these studies focus on the production of bioetanol or biogas; reports of other molecules such as succinic acid, furfural, polyhydroxyalkanoates and bisabolene were also found. Industrial viability of these processes remains a question, since pretreatment, hydrolysis and final conversion steps are usually expensive. It necessary that future studies focus on optimizing conditions of these processes as well as making them green, ensuring that they can be scaled.

Mercury (II) removal from aqueous solutions by iron nanoparticles synthesized from extract of Eucalyptus grandis.

Artisanal mining is the main source of mercury emissions in South America, which generates a serious environmental impact due to this toxic metal, recent research is directed to minimize the impact, therefore this study focuses on the green synthesis of nanoparticles for the absorption of mercury in water. For the synthesis of iron nanoparticles, an extract of Eucalyptus grandis was used with iron chloride salts using water as solvent. The synthesized nanoparticles showed a specific surface area of 131.90 m2/g, determined by Brunauer-Emmett-Teller isotherm (BET). Nanoparticles were characterized by Fourier transformed infrared spectroscopy (FTIR) and transmission electron microscopy (MET). The behavior of nanoparticles synthesized during Hg (II) retention was evaluated measuring pH, temperature, nanoparticle dosing, presence of other ions and comparing with other adsorbents. All analyses measured by atomic absorption spectroscopy by the cold vapor technique (CVAAS), presenting a retention percentage for Hg (II) between 75.05 and 79.59% with pH between 4 and 7. The adsorption isothermal was adjusted to the Freundlich model and the percentage of retention of Hg by the synthesized nanoparticle was 79.26%. This work shows a method for obtaining an environmentally friendly mercury adsorbent from iron and E. grandis with a mercury retention capacity comparable to commercial adsorbents.

A critical review on paracetamol removal from different aqueous matrices by Fenton and Fenton-based processes, and their combined methods.

Paracetamol (PCT), also known as acetaminophen, is a drug used to treat fever and mild to moderate pain. After consumption by animals and humans, it is excreted through the urine to the sewer systems, wastewater treatment plants, and other aquatic/natural environments. It has been detected in trace amounts in effluents of wastewater plant treatments, sewage sludge, hospital wastewaters, surface waters, and drinking water. PCT can cause genetic code damage, oxidative degradation of lipids, and denaturation of protein in cells, and its toxicity has been well-proven in bacteria, algae, macrophytes, protozoan, and fishes. To avoid its harmful health problems over living beings, powerful Fenton and Fenton-based treatments as pre-eminent advanced oxidation processes (AOPs) have been developed because of the inefficient treatment by conventional treatments. This paper presents a comprehensive and critical review over the application of such Fenton technologies to remove PCT from natural waters, synthetic wastewaters, and real wastewaters. The characteristics and main results obtained using Fenton, photo-Fenton, electro-Fenton, and photoelectro-Fenton are described, making special emphasis in the oxidative action of the generated reactive oxygen species. Hybrid processes based on the coupling with ultrasounds, gamma radiation, photocatalysis, photoelectrocatalysis, zero-valent iron-activated persulfate, adsorption, and microbial fuel cells, are analyzed. Sequential treatments involving the initiation with plasma gliding arc discharge and post-biological process are detailed. Comparative results with other available AOPs are also described and discussed. Finally, 13 aromatic by-products and 9 short-linear aliphatic carboxylic acid detected during the PCT removal by Fenton and Fenton-based processes are reported, with the proposal of three parallel pathways for its initial degradation.

Effect of enzymatic hydrolyzed protein from pig bones on some biological and functional properties.

Pig bone residue is considered a potential source of hydrolysates from its protein with added value uses in the food industry. This work deals with the enzyme hydrolysis of pig bone protein. The conditions for extracting the protein hydrolysate were optimized and the equation obtained allowed samples with different degrees of hydrolysis (DH) to be extracted to study how the biological properties of in-vitro hydrolized protein affected digestibility, determination of the inhibitory activity of the angiotensin-converting enzyme and the antioxidant activity and its functional properties. It was found that the emulsifying capacity and emulsion stability increased at intermediate DH values, after which these properties decreased with the increase in DH. The in-vitro digestibility and angiotensin-converting enzyme (ACE) of the hydrolysates are also clearly affected by the DH. The amino acid composition of the hydrolized protein is also determined.

Characterization and determination of the quality of rosins and turpentines extracted from Pinus oocarpa and Pinus patula resin.

Rosins and turpentines present in pine resins have been widely used both industrially (coatings, electronics and paint) and pharmaceuticals (ointments). Among the main components of these matrices is abietic acid. This study focuses on the characterization and evaluation of the quality of rosins and turpentines in addition to the quantification of abietic acid in rosins. Rosin and spirit of turpentine were obtained separately through the distillation method from P patula and P. oocarpa resin, species grown in the Department of Cauca-Colombia. Resin-tapping was made using the traditional method (cup and gutter). Quality indicators were determined according to ASTM standards. Solubility tests and identification of functional groups were performed on the obtained rosin by ultraviolet-visible spectroscopy (UV-Vis), infrared (IR) and nuclear magnetic resonance (1H-NMR). The abietic acid present in the rosins was determined by high performance liquid chromatography (HPLC). According to their high acid value and low percentage of unsaponifiable matter, the extracted rosins are considered of medium-high quality. Quantification of abietic acid by HPLC showed 14.85 ± 0.24% and 16.09 ± 0.11% for P. patula and P. oocarpa rosin respectively.

Enzymatic hydrolysis as a tool to improve total digestibility and techno-functional properties of pigeon pea (Cajanus cajan) starch.

Recent studies have indicated that starch from legumes can potentially be used as an alternative to commercial flour with applications in food and biomaterials; however, some modifications may be required first to improve their functionality, as they show relatively lower solubility and functional properties compared to commonly marketed flours (e.g. good water retention capacity). This work used multiple enzymes in flour extracts of pigeon pea (Cajanus cajan), a legume, to optimize the enzyme hydrolysis process of such extracts by the Response Surface Method (RSM), to increase the digestibility and obtain desirable functional attributes at the nutritional level. The pH, temperature, time and enzyme/substrate (E/S) ratio were evaluated, and the degree of hydrolysis (DH) was calculated as well as the reducing sugar content (%RS), used as response variable. According to the experimental design, the best pH, temperature, time and E/S ratio were 6.8, 43 °C, 1.84% m/m and 270 min, respectively. The %RS for the samples under optimal conditions was 3.49 ± 0.02%, and the in vitro digestibility yielded values of 39.2 ± 0.4, 58.6 ± 0.3 and 2.2 ± 0.2 for slowly digestible starch (SDS), rapidly digestible starch (RDS) and resistant starch (RS), respectively. Total digestibility (TD) was 97.8 ± 0.5. The statistical analysis revealed a strong positive relationship for E/S ratio followed by pH: (E/S) ratio, temperature and pH. Enzymatic hydrolysis carried out on pigeon pea showed an increase in TD. Viscosity, water retention capacity (WRC) and solubility were evaluated showing good response for future applications at the industrial level.

EFECTO DEL pH EN LAS TASAS DE BIOACUMULACIÓN DE METALES PESADOS EN LA MACROALGA Bostrychia calliptera (Rhodomelaceae, Ceramiales) / Effect of pH on the bioacumulation rates of heavy metals in macroalgae Bostrychia calliptera (Rhodomelaceae, Ceramiales)

RESUMEN Uno de los factores que más influye en las características químicas de un metal en solución es el nivel de acidez. El pH, por lo tanto, afecta la reactividad del ion y por ende su interacción con los puntos de unión de la pared celular de la planta. Este estudio evaluó el efecto del pH en la capacidad de bioacumulación de metales pesados en el alga roja Bostrychia calliptera (Rhodophyta, Rhodomelaceae). Se sometieron talos del alga a diferentes concentraciones de mercurio (Hg) y Plomo (Pb), desde 0,1 hasta 10 mg/L para Hg y desde 0,1 hasta 15 mg/L para Pb, durante periodos exposición de 0, 12, 24 y 96 horas, bajo diferentes niveles de pH. Las concentraciones de metal acumulado se determinaron por espectrofotometría de absorción atómica. Las mayores tasas de acumulación se encontraron en el alga expuesta a pH 8 (tanto para Hg como para Pb), el cual es un nivel de pH muy cercano al medido en el área de muestreo. La concentración de metal en el alga se incrementó de manera lineal hasta las 48 h de exposición, tiempo en el que se evidenció una mayor eficiencia de acumulación durante el primer intervalo del periodo del bioensayo. El presente estudio permitió identificar el uso potencial del alga B. calliptera como especie bioindicadora de metales pesados en ambientes estuarinos.

ABSTRACT One of the factors with a bigger influence on the chemical characteristics of metal in solution is the level of acidity. Solution pH affects the cell wall metal-binding sites and the metal ion chemistry in water. This study evaluated the effect of pH on the bioaccumulation capacity in the red algae B. calliptera (Rhodophyta, Rhodomelaceae) exposed to different pH ranges. Algae thalli were subjected to different concentrations ofmercury (Hg) and Lead (Pb), at concentrations from 0.1 to 10 mg/L for Hg and from 0.1 to 15 mg/L for Pb, respectively, during the following exposure times: 0, 12, 24 and 96 hours for each ion. Metal concentrations were determined by atomic absorption spectrophotometry according to standard APHA methods. The highest accumulation rates were found when the algae were exposed to pH 8 (for both Hg and Pb), which is a level very close to that measured in the study area. The metal concentration in the algae increased linearly until 48 hrs, a time where a greater accumulation efficiency was evident. The present study allowed to identify the potential use of the alga B. calliptera as a bioindicator species for heavy metals in estuarine environments.

Controlled Branching by Step-Growth Polymerization of Xylitol and Succinic Acid via Microwave Irradiation.

Copolymerization of xylitol usually yields cross-linked materials. In this work, microwave-assisted polyesterification of xylitol and succinic acid produced materials with diverse molecular weights and different branching degrees, and more importantly, no cross-linking was observed, as supported by the solubility behavior and spectroscopic data. Reactions were carried out for short times, less than 20 min, which is not common for production of industrial polyesters. Control over the branching degree was achieved by tuning the reaction conditions, such as temperature, time of exposure, and monomer ratio, during microwave irradiation. No solvent or catalyst was employed during the step-growth polymerization.

Lipasas en síntesis de polímeros: avances y contribución a la química verde de polímeros / Lipases in polymer synthesis: advantages and its contribution to green polymer chemistry

RESUMEN Las lipasas han sido usadas en las últimas décadas como catalizadores eficientes en la síntesis enzimática de polímeros y gracias a características como alta selectividad, reciclabilidad, inocuidad y fácil separación/purificación se han convertido en una herramienta importante en el campo de los polímeros. En este trabajo se recopilan los desarrollos más importantes en el área y a su vez se muestra la tendencia actual de este campo de investigación.

ABSTRACT Lipases have been used in last decades as efficient catalysts in enzimatic polymer chemistry, thanks to its high selectivity, recyclabil-ity, safety and easy recovery/ separation, lipases have become in an important tool in polymer field. In this paper we compile the most important achievements in the enzimatic polymer chemistry and, at the same, time we show the current trend in this field of research.

Determinación y comparación cualitativa de cannabinoides presentes en productos naturales comerciales del departamento del Cauca, Colombia / Determination and qualitative comparison of cannabinoids present in commercial natural products of the Cauca Department-Colombia

RESUMEN Actualmente, hay un creciente interés por el estudio de Cannabis sativa y sus componentes ya que se le atribuye propiedades terapéuticas en el tratamiento de enfermedades. En Colombia y específicamente en el departamento del Cauca se comercializan productos de cannabis tanto para fines no medicinales como terapéuticos. En consecuencia, es necesario el análisis de estos productos de manera que se pueda conocer la composición de los mismos y el posible efecto que pueda tener sobre la salud. El análisis de los componentes de estos productos se llevó a cabo empleando la cromatografía líquida de alta resolución (CLAR) y espectrometría de masas (EM), de tal manera que permitieron la identificación de las principales especies cannabinoides; Δ9-tetra hidrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). La separación de los analitos se llevó a cabo mediante la implementación de una columna analítica C18 de fase reversa, elución isocrática 1 mL/ min, presión del sistema 800 PSI, una mezcla de acetonitrilo ACN y buffer fosfato (KHPO4) en relación 65/35 como fase móvil, volumen de inyección de 10 µL, un tiempo de análisis de 15 min, y detección a 220 nm.

SUMMARY Cannabis sativa has now experienced an increasing interest in the study of its components since it is attributed therapeutic properties in the treatment of diseases. In Colombia and specifically in the Cauca Department, Cannabis products are marketed both for non-medicinal and therapeutic purposes. Consequently, it is necessary to analyze these products in such a way that the composition of the products and their possible effect on health can be known. The analysis ofthe components of these products was carried out using high performance liquid chromatog-raphy (HPLC) and mass spectrometry (MS), in such a way that they allowed the identification of the main cannabinoid species; Δ9-tetra hydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). The separation of the analytes was carried out by means of the implementation of a reverse phase C18 analytical column, isocratic elution 1 mL/min, system pressure 800 PSI, a mixture of acetonitrile ACN and phosphate buffer (KHPO4) in relation 65/35 as mobile phase, injection volume of10 µL, analysis time of15 min, and detection at 220 nm.

Saponinas de quinua (Chenopodium quinoa Willd.): un subproducto con alto potencial biológico / Saponins of Quinoa (Chenopodium quinoa Willd.): a by-product with high biological potential

Las saponinas son un tipo de metabolito secundario ampliamente estudiado por sus reconocidas propiedades biológicas. Gran parte de las investigaciones en fitoquímica están dirigidas a encontrar nuevas fuentes naturales de saponinas con aplicación medicinal. La quinua (Chenopodium quinoa Willd.) es una planta que ha alcanzado un valioso reconocimiento por ser una fuente de alimentos altamente nutritivos, así como una especie rica en saponinas triterpénicas contenidas, principalmente, en la cáscara de las semillas. A la fecha, se han identificado alrededor de 30 saponinas derivadas de la hederagenina y de los ácidos oleanólico, fitolacagénico y serjanico en la planta. El consumo del grano de quinua implica la remoción de la cáscara a fin de reducir su sabor amargo, la ingesta de niveles residuales de saponinas y la obtención de un subproducto rico en las mismas. Esta revisión, inicialmente, ofrece una contex-tualización general de las saponinas; posteriormente, recopila las características estructurales de las saponinas identificadas en la quinua, describe el efecto del procesamiento del grano en su contenido de saponinas y, finalmente, expone los efectos biológicos explorados con extractos de saponinas de quinua, los cuales pueden ser considerados como punto de partida en investigaciones futuras dirigidas al fortalecimiento de su uso en el campo farmacéutico y/o nutracéutico.

Saponins are a type of secondary metabolite that have been widely studied due to their recognized biological properties. Most research into phytochemical has focused on finding new natural sources of saponins with medicinal interest. Quinoa ( Chenopodium quinoa) is a plant that has attained importance as a valuable source of food highly nutritious and rich in triterpenes saponins which are mainly in the outer husks of the seeds. Up to date, about 30 saponins derived from hederagenin, oleanolic acid, phytolaccagenic acid, and serjanic acid have been identified in the plant. Quinoa consumption involves removal of the husk to reduce its bitter taste, the ingestion of residual levels of saponins and obtaining a product rich in saponins. This revision, initially, offers a general contextualization of saponins, then, gathers the structural features of identified saponins in quinoa, describes the effect of the processing of the grain on its saponins content, and finally, exposes the biological properties explored with quinoa saponins extracts which might be considered as a starting point for future investigations aimed at strengthening of their use in the pharmaceutical and/or nutraceutical field.

Campos electromagnéticos planares permiten explicar transducción en receptores de células T / Use of planar electromagnetic fields to explain transduction in T-cell receptors / Campos eletromagnéticos planares permitem explicar transdução em receptores de células T

El acople de un ligando con un receptor induce una señal que viaja a través de este último hasta llegar a su dominio intracelular, donde desencadena una cascada de respuesta. Analizando el acople del Receptor de Células T (TCR) con antígenos foráneos, los autores identificaron patrones moleculares de geometría planar al interior de este receptor, capaces de internalizar la señal producida por el acople TCR/Antígeno. Este mecanismo fue también hallado en diversidad de sistemas receptor-ligando de diferente funcionalidad biológica, tales como las parejas Bomba de Calcio-ADP, el acople viral gp120-CD4 y el sistema Hemoglobina-Oxígeno. Dicho mecanismo identificado por los autores es de naturaleza Cuántica y permitiría explicar la transducción de señales en todo tipo de receptores bioquímicos. Este hallazgo facilitaría el diseño de péptidos-vacuna con alta capacidad inmunogénica así como el desarrollo de nuevos medicamentos.

The coupling of a ligand with a receptor induces a signal that travels through the receptor until it reaches the intracellular domain, where it triggers a response cascade. By analyzing the coupling of receptor cells (TCR) with foreign antigens, the authors identified the presence of molecular patterns, planar in geometry, within this receptor, that are capable of internalizing the signal produced by TCR/antigen coupling. This mechanism, also found in a range of receptor-ligand systems with greatly differing biological functions, including calcium pump-ADP, gp120-CD4 viral coupling, and the hemoglobin-oxygen system, is quantum in nature and capable of explaining the means of signal transduction in all kinds of biochemical receptors. As such, the finding may facilitate the design of vaccine-peptides with high immunogenicity, as well as make it possible to develop new drugs.

O acoplamento de um ligante com um receptor induz um sinal que viaja através do receptor atingindo seu domínio intracelular onde desencadeia uma cascata de resposta. Analisando o acoplamento do Receptor de Células T (TCR) com antígenos forâneos, os autores identificaram padrões moleculares de geometria planar no interior desse receptor, capazes de internalizar o sinal produzido pelo acoplamento TCR/ Antígeno. Esse mecanismo também foi encontrado em múltiplos sistemas receptor-ligante de diferente funcionalidade biológica, tais como os pares Bomba de Cálcio-ADP, o acoplamento viral gp120-CD4 e o sistema de Hemoglobina-Oxigênio. Tal mecanismo identificado pelos autores é de natureza Quântica e permitiria explicar a transdução de sinais em todo tipo de receptores bioquímicos. Este achado também facilitaria o desenho de peptídeos-vacina com alta capacidade imunogênica bem como o desenvolvimento de novos medicamentos.

Evaluación de la capacidad antioxidante y metabolitos secundarios de extractos de dieciséis plantas medicinales / Evaluation of antioxidant capacity and secondary metabolites of sixteen medicinal plants extracts

El presente estudio evaluó la capacidad antioxidante de los extractos de dieciséis plantas medicinales: escoba amarga (Parthenium hysterophons), ajenjo (Artemisia absinthium), guarumo (t), chaya (Cnidoscolus chayamansa), borraja (Borago officinalis), balsa (Ochroma sp.), linaza (Linum usitatissimum), hierba Luisa (Cymbopogon citratus), toronjil (Melissa officinalis), buganvilla (Bougainvillea spectabilis), alcachofa (Cynara scolymus), guaviduca (Piper carpunya), altamisa (Ambrosia cumanensis), diente de león (Taxacum officinales), buscapina (Parietaria officinalis) y moringa (Moringa oleifera). Para ello, se usó el método DPPH (radical 1,1-difenil-2-picrilhidrazil); además, se realizaron ensayos de reconocimiento de metabolitos secundarios a fin de obtener los primeros indicios de compuestos de interés fitoquímico. La actividad captadora de radicales libres de los extractos se expresó como valor de IC50 (µg/mL) (cantidad necesaria para inhibir la formación de radicales DPPH en un 50%). El valor bajo de IC50 refleja mejor acción eliminadora de radicales libres. Aunque la mayoría de las muestras evaluadas mostraron buena capacidad antioxidante con este método (DPPH), los ensayos de los extractos hidro-alcohólicos demuestran que la alcachofa (IC50 9,89 µg/mL), moringa (IC50 11,4 µg/mL) y borraja (IC50 14,0 µg/mL) presentaron mayor capacidad antioxidante. Mediante las pruebas químicas de caracterización, se detectó la presencia de flavonoides, taninos, triterpenos, alcaloides y saponinas en la mayoría de las especies analizadas (aproximadamente 56-69%); tan sólo un 20% de las mismas mostró la presencia de polifenoles, glucósidos cianogénicos, lactonas, cumarinas, esteroles y antraquinonas. Según los resultados, se podría considerar a estas plantas como fuentes prometedoras de metabolitos secundarios con actividad antioxidante. ABSTRACTThis study evaluated the antioxidant capacity of sixteen medicinal plants: Escoba amarga (Parthenium hysterophons), ajenjo (Artemisia absinthium), guarumo (Cecropia obtusifolia), chaya (Cnidoscolus chayamansa), borraja (Borago officinalis), balsa (Ochroma sp.), linaza (Linum usitatissimum), hierba Luisa (Cymbopogon citratus), toronjil (Melissa officinalis), buganvilla (Bougainvillea spectabilis), alcachofa (Cynara scolymus), guaviduca (Piper carpunya), altamisa (Ambrosia cumanensis), diente de León (Taxacum officinales), buscapina (Parietaria officinalis)and moringa (Moringa oleifera). For this, the DPPH (radical 1, 1-difenil-2-picrilhidrazil) method was used; furthermore, recognition assays of secondary metabolites were performed, in order to obtain the first signs of phytochemical compounds of interest. The free radical scavenging activity of the extracts was expressed as IC50 value (g/mL) (necessary amount to inhibit the formation of 50% of DPPH radical). The low value of IC50 reflects better free radical scavenging action. Although most of the samples tested showed good antioxidant capacity with this method (DPPH), tests of hydroalcoholic extracts show that alcachofa (IC50 9.89 mg/mL), moringa (IC50 11.4 mg/mL) and borraja (IC50 14.0 mg/mL) were those with higher antioxidant capacity. Through chemical characterization tests, the presence of flavonoids, tannins, triterpenes, alkaloids and saponins were detected in most of the analyzed species (approximately 56-69%); only 20% of them showed the presence of polyphenols, cyanogenic glycosides, lactones, coumarins, anthraquinones and sterols. According to the results obtained, these plantsmight be considered as promising sources of secondary metabolites with antioxidant activity.

Hallazgo de patrones para péptidos-vacuna con capacidad de acople universal en moléculas de HLA-II / Identification of patterns for peptide-vaccines in universal capacity coupling HLA-II molecules / Identificagáo de padroes para peptídeos-vacina com capacidade de acoplamento universal em moléculas HLA-II

Partiendo del alineamiento múltiple de secuencias proteicas humanas obtenidas de las bases de datos del National Center of Biotechnology Information (NCBI) y su posterior análisis espacial tridimensional, se estableció la existencia de un patrón de acople universal para péptidos presentados por las moléculas de histocompatibilidad HLA-II (DR, DP y DQ), siendo una base para el diseño de vacunas proteicas. Estos patrones espaciales fueron claramente exhibidos por los residuos altamente conservados de los tres tipos de moléculas de HLA-II. La aplicación de este nuevo hallazgo permitió diseñar péptidos con mejores valores de acople péptido-HLA-II, que los generados por el péptido de acople universal conocido como CLIP (class Il-associated invariant chain peptide).

Starting from the multiple alignment of human protein sequences obtained from the NCBI database (National Center of Biotechnology Information) and subsequent three-dimensional spatial analysis, the existence of a pattern of universal coupling to peptides presented by MHC molecules HLA-II (DR, DP and DQ) was established, being a basis for the design of protein vaccines. These spatial patterns were clearly exhibited by highly conserved residues of the three kinds of HLA-II molecules. The application of this new finding made it possible to design peptides with better Peptide -HLA-II coupling values than those generated by the universal coupling peptide called CLIP (class II-associated invariant chain peptide).

FA partir do alinhamento múltiplo de sequéncias de proteínas humanas obtidas a partir das bases de dados do NCBI (National Center of Biotechnology Information) e análise espacial tridimensional subsequente, estabeleceu-se a existéncia de um padráo de acoplamento universal para peptídeos apresentados pelas moléculas de histocompatibilidade HLA-II (DR, DP e DQ), sendo uma base para o desenho de vacinas proteicas. Estes padroes espaciais foram claramente exibidos pelos residuos altamente conservados dos trés tipos de moléculas de HLA-II. A aplicagáo deste novo achado permitiu desenhar peptídeos com melhores valores de acoplamento peptídeo-HLA-II, do que aqueles gerados pelo peptídeo de acoplamento universal conhecido como CLIP (classe II-peptídeo associado a cadeia invariante).

Hallazgo de patrones para péptidos-vacuna con capacidad de acople universal en moléculas de HLA-II / Identification of patterns for peptide-vaccines in universal capacity coupling HLA-II molecules / Identificagáo de padroes para peptídeos-vacina com capacidade de acoplamento universal em moléculas HLA-II

Partiendo del alineamiento múltiple de secuencias proteicas humanas obtenidas de las bases de datos del National Center of Biotechnology Information (NCBI) y su posterior análisis espacial tridimensional, se estableció la existencia de un patrón de acople universal para péptidos presentados por las moléculas de histocompatibilidad HLA-II (DR, DP y DQ), siendo una base para el diseño de vacunas proteicas. Estos patrones espaciales fueron claramente exhibidos por los residuos altamente conservados de los tres tipos de moléculas de HLA-II. La aplicación de este nuevo hallazgo permitió diseñar péptidos con mejores valores de acople péptido-HLA-II, que los generados por el péptido de acople universal conocido como CLIP (class Il-associated invariant chain peptide).(AU)

Starting from the multiple alignment of human protein sequences obtained from the NCBI database (National Center of Biotechnology Information) and subsequent three-dimensional spatial analysis, the existence of a pattern of universal coupling to peptides presented by MHC molecules HLA-II (DR, DP and DQ) was established, being a basis for the design of protein vaccines. These spatial patterns were clearly exhibited by highly conserved residues of the three kinds of HLA-II molecules. The application of this new finding made it possible to design peptides with better Peptide -HLA-II coupling values than those generated by the universal coupling peptide called CLIP (class II-associated invariant chain peptide).(AU)

FA partir do alinhamento múltiplo de sequéncias de proteínas humanas obtidas a partir das bases de dados do NCBI (National Center of Biotechnology Information) e análise espacial tridimensional subsequente, estabeleceu-se a existéncia de um padráo de acoplamento universal para peptídeos apresentados pelas moléculas de histocompatibilidade HLA-II (DR, DP e DQ), sendo uma base para o desenho de vacinas proteicas. Estes padroes espaciais foram claramente exibidos pelos residuos altamente conservados dos trés tipos de moléculas de HLA-II. A aplicagáo deste novo achado permitiu desenhar peptídeos com melhores valores de acoplamento peptídeo-HLA-II, do que aqueles gerados pelo peptídeo de acoplamento universal conhecido como CLIP (classe II-peptídeo associado a cadeia invariante).(AU)

Identification and confirmation of differentially expressed fucosylated glycoproteins in the serum of ovarian cancer patients using a lectin array and LC-MS/MS.

In order to discover potential glycoprotein biomarkers in ovarian cancer, we applied a lectin array and Exactag labeling based quantitative glycoproteomics approach. A lectin array strategy was used to detect overall lectin-specific glycosylation changes in serum proteins from patients with ovarian cancer and those with benign conditions. Lectins, which showed significant differential response for fucosylation, were used to extract glycoproteins that had been labeled using isobaric chemical tags. The glycoproteins were then identified and quantified by LC-MS/MS, and five glycoproteins were found to be differentially expressed in the serum of ovarian cancer patients compared to benign diseases. The differentially expressed glycoproteins were further confirmed by lectin-ELISA and ELISA assay. Corticosteroid-binding globulin (CBG), serum amyloid p component (SAP), complement factor B (CFAB), and histidine-rich glycoprotein (HRG) were identified as potential markers for differentiating ovarian cancer from benign diseases or healthy controls. A combination of CBG and HRG (AUC = 0.825) showed comparable performance to CA125 (AUC = 0.829) in differentiating early stage ovarian cancer from healthy controls. The combination of CBG, SAP, and CA125 showed improved performance for distinguishing stage III ovarian cancer from benign diseases compared to CA125 alone. The ability of CBG, SAP, HRG, and CFAB to differentiate the serum of ovarian cancer patients from that of controls was tested using an independent set of samples. Our findings suggest that glycoprotein modifications may be a means to identify novel diagnostic markers for detection of ovarian cancer.

Structural requirements for mitotane activity: development of analogs for treatment of adrenal cancer.

AIM: Mitotane is used in adrenal cancer as adjuvant therapy, monotherapy or combined with other cytotoxic agents in advanced disease, but only 30% of patients respond. The aim of this study was to define the structural requirements for drug activity and to develop analogs with improved adrenalytic action. MATERIALS AND METHODS: Nine analogs of [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2dichloroethane] (o,p'-DDD) were tested by measuring suppression of cortisol secretion and the presence of inflammatory changes in the dog adrenal and inhibition of cell proliferation and cortisol production by NCI-H295 human adrenal cancer cells. RESULTS: In addition to mitotane, o,p'-DDClBr and o,p'-DDBr(2), were active in vitro and in vitro: Their effects were comparable to that of o,p'-DDD when tested at 50 µM concentration, but o,p'DDBr(2) was significantly more active at the lower 20 µM concentration. CONCLUSION: A dihalogenated methine carbon is required for adrenalytic activity. A change in the aromatic portion of the mitotane molecule causes loss of activity. Because of its greater activity at lower concentrations, o,p'-DDBr(2) has potential application in the treatment of patients with adrenal cancer.

Quantifying massive allograft healing of the canine femur in vivo and ex vivo: a pilot study.

BACKGROUND: Allograft integration in segmental osseous defects is unpredictable. Imaging techniques have not been applied to investigate angiogenesis and bone formation during allograft healing in a large-animal model. QUESTIONS/PURPOSES: We used dynamic contrast-enhanced (DCE)-MRI and cone beam (CB)-CT to quantify vascularity and bone volume in a canine femoral allograft model and determined their relationship with biomechanical testing and histomorphometry. METHODS: Femoral ostectomy was performed in three dogs and reconstructed with a 5-cm allograft and compression plate. At 0.5, 3, and 6 months, we performed DCE-MRI to quantify vascular permeability (Ktrans) and perfused fraction and CB-CT to quantify bone volume. We also performed posteuthanasia torsional testing and dynamic histomorphometry of the grafted and nonoperated femurs. RESULTS: DCE-MRI confirmed the avascular nature of allograft healing (perfused fraction, 2.08%-3.25%). CB-CT demonstrated new bone formation at 3 months (26.2, 3.7, and 2.2 cm(3)) at the graft-host junctions, which remodeled down at 6 months (14.0, 2.2, and 2.0 cm(3)). The increased bone volume in one subject was confirmed with elevated Ktrans (0.22) at 3 months. CB-CT-identified remodeled bone at 6 months was corroborated by histomorphometry. Allografted femurs recovered only 40% of their strength at 6 months. CONCLUSIONS: CB-CT and DCE-MRI can discriminate differences in angiogenesis and bone formation in the canine allograft model, which has potential to detect a small (32%) drug or device effect on biomechanical healing with only five animals per group.

Enhancement of breast calcification visualization and detection using a modified PG method in Cone Beam Breast CT.

Cone Beam Breast CT is a promising diagnostic modality in breast imaging. Its isotropic 3D spatial resolution enhances the characterization of micro-calcifications in breasts that might not be easily distinguishable in mammography. However, due to dose level considerations, it is beneficial to further enhance the visualization of calcifications in Cone Beam Breast CT images that might be masked by noise. In this work, the Papoulis-Gerchberg method was modified and implemented in Cone Beam Breast CT images to improve the visualization and detectability of calcifications. First, the PG method was modified and applied to the projections acquired during the scanning process; its effects on the reconstructed images were analyzed by measuring the Modulation Transfer Function and the Noise Power Spectrum. Second, Cone Beam Breast CT images acquired at different dose levels were pre-processed using this technique to enhance the visualization of calcification. Finally, a computer-aided diagnostic algorithm was utilized to evaluate the efficacy of this method to improve calcification detectability. The results demonstrated that this technique can effectively improve image quality by improving the Modulation Transfer Function with a minor increase in noise level. Consequently, the visualization and detectability of calcifications were improved in Cone Beam Breast CT images. This technique was also proved to be useful in reducing the x-ray dose without degrading visualization and detectability of calcifications.