In silico evaluation of new mangiferin-based Positron Emission Tomography radiopharmaceuticals through the inhibition of metalloproteinase-9.

Metalloproteinase-9 (MMP-9) is a key protein in cancer advancement and metastasis owing to its ability to degrade some extracellular matrix components. Mangiferin, a natural polyphenolic compound, has demonstrated through experimental and theoretical studies to be a great anticancer agent for the selective inhibition of MMP-9. This work aimed to evaluate the utility of several fluorinated compounds obtained from MF as possible Positron Emission Tomography (PET) radiopharmaceuticals oriented to MMP-9. Density Functional Theory calculations of MF were made to obtain the most active sites toward electrophilic and nucleophilic reactions and propose a synthetic route to produce its fluorinated derivatives. The reactivity study allowed us to propose a late-stage synthetic route based on click chemistry to obtain three fluorinated MF-based derivatives. Molecular docking calculations suggested that the derivative F-propyl-MF could be suitable as PET radiopharmaceutical owing to the establishment of a five-coordinated complex with the catalytic Zn atom belonging to the active site of MMP-9, crucial factor in the inhibition of MMP-9.

Explaining the interaction of mangiferin with MMP-9 and NF-ƙß: a computational study.

Mangiferin is a glycosylated xanthone widely distributed in nature, which exhibits wide pharmacological activities, highlighting its anti-cancer properties. Mangiferin interferes with inflammation, lipid, and calcium signaling, which selectively inhibits multiple NFkB target genes as interleukin-6, tumor necrosis factor, plasminogen, and matrix metalloproteinase, among others. In this work, the interactions of this polyphenol with MMP-9 and NF-κß are characterized by using computational chemistry methods. The results show MMP-9 inhibition by mangiferina is characterized for the interact with the catalytic Zn atom through a penta-coordinate structure. It is also demonstrated through a strong charge transfer established between mangiferin and Zn in the QM/MM study. Concerning the mangiferin/NF-κß system, the 92.3% of interactions between p50 sub-unity and DNA are maintained with a binding energy of - 8.04 kcal/mol. These findings indicate that mangiferin blocks the p50-p65/DNA interaction resulting in the loss of the functions of this hetero-dimeric member and suggesting inhibition of the cancer progression. Experimental results concerning the anti-cancer properties of mangiferin show that this natural compound can inhibit selectively MMP-9 and NF-ƙß. Although the anti-tumor properties of mangiferin are well defined, its molecular mechanisms of actions are not described. In this work, a computational study is carried out to characterize the interactions of mangiferin with these molecular targets. The results obtained corroborate the anti-proliferative and anti-apoptotic activity of mangiferin and provide a depiction of its mechanisms of action.

In silico development of new PET radiopharmaceuticals from mTOR inhibitors.

Rapamycin (or sirolimus) is a macrolide that has shown to be useful as an immunosuppressant and that was studied in metabolic, neurological, or genetic disorders. Rapamycin is a specific natural inhibitor of the mechanistic target of rapamycin (mTOR) that is a kinase protein playing a pivotal role in cell growth and proliferation by activation of several metabolic processes. This work aimed to evaluate the utility of several compounds obtained from rapamycin and its semi-synthetic analogs everolimus and temsirolimus as possible radiopharmaceuticals oriented to this protein. Density Functional Theory calculations of these molecules were made and further analysis of the dual descriptor, charges populations, and of the electrostatic potential surfaces were performed. Molecular docking simulations were used to evaluate the interactions of the rapamycin with the studied candidates. They allowed us to propose two strategies for the synthesis of novel compounds based on electrophilic reactions. Molecular docking results also helped us to eliminate molecules that did not interact correctly with the target. Finally, we found for the first time, that the novel compounds synthesized through the electrophilic addition reaction that employed 18F-selectfluor, should maintain the biological activity of original compounds and could be suitable as Positron Emission Tomography radiopharmaceuticals targeting mTOR Complex1 system.

SARS-CoV-2 en aguas residuales y superficiales: ¿cómo lidiar con el problema? / Sars-cov-2 in wastewater and surface water: how to deal with the problem?

Introducción: hoy la humanidad sufre uno de los peores episodios debido a la pandemia causada por el SARS-CoV-2. Su alta infectividad, rápida propagación y persistencia en ciertas superficies dificultan el combate de este virus. Su presencia en aguas residuales y posible transmisión fecal-oral podría ser una nueva amenaza para la salud pública. Objetivo: alertar a la comunidad científica internacional y a los gobiernos sobre la presencia de SARS-CoV-2 en las aguas residuales y sobre qué hacer para evitar su propagación por este medio. Métodos: se realizó una revisión de artículos referenciados en SCOPUS y Web of Science desde el año 2019 relacionados con la presencia del virus en aguas residuales y superficiales. Resultados y discusión: es necesario establecer sistemas de monitoreo, utilizar métodos analíticos sensibles y rápidos para la detección del virus en las aguas residuales y superficiales. Asimismo, implantar protocolos de inactivación del virus en las unidades de salud y en las plantas de tratamiento de aguas. Se recomiendan procesos con oxidantes químicos, radiación ultravioleta, fotocatálisis, foto-Fenton, ozono o filtración por membrana. Además, se debe alertar a la población sobre la importancia del lavado y de la desinfección de productos agrícolas, así como del cuidado en su manejo por parte de los trabajadores agrícolas

Introduction: Today, humanity suffers one of the worst episodes due to a pandemic caused by the SARS-CoV-2. Its high infectivity and rapid spread combined with its persistence on certain surfaces difficult to fight this virus. Its presence in wastewater and possible fecal-oral transmission could be a new public health threat. Objective: To alert the international scientific community and governments about the presence of SARS-CoV-2 in wastewater, and what to do to prevent its spread by this means. Methods: A review of articles referenced in SCOPUS and Web of Science since 2019 related to the presence of the virus in wastewater and surface water was performed. Results and discussion: It is necessary to establish monitoring systems with the use of sensitive and rapid analytical methods for the on-site detection of viruses in wastewaters and surface waters. It should be established virus inactivation protocols at the health units, and water treatment plants, where are recommended processes with chemical oxidants, ultraviolet radiation, photocatalysis, photo-Fenton, ozone, or membrane filtration. It is necessary to alert the population about the importance of washing and disinfecting agricultural products, mainly vegetables and fruits, as well as the care in its handling by agricultural workers

Caracterización clínica, endoscópica e histológica del cáncer colorrectal en un grupo de pacientes cubanos / Clinical, endoscopic and histological characterization of colorectal cancer in a group of Cuban patients

Introducción: el cáncer colorrectal representa el tercero en incidencia en ambos sexos a nivel mundial, por ellos es importante realizar estudios epidemiológicos del mismo. Objetivo: caracterizar clínica, endoscópica e histológicamente el cáncer colorrectal en pacientes atendidos en el Centro de Investigaciones Médico Quirúrgicas, Cuba. Métodos: estudio observacional, descriptivo y retrospectivo a 52 pacientes (31 hombres y 21 mujeres) con cáncer colorrectal diagnosticados entre 2012 y 2014. Se recolectaron los datos de historias clínicas y estudios endoscópicos, imagenológicos y anatomopatológicos. La media de edad fue 66,73 años. Resultados: el antecedente y/o presencia de pólipos en el colon predominó con 55.8 %. La enterorragia se presentó en 38.5 %, la oclusión intestinal y el dolor abdominal en 17.3 %. Durante la colonoscopia, se encontró el 47.7% con lesión ulcerada y el lugar más comprometido fue el colon descendente. El adenocarcinoma se encontró en 90.4 % de los pacientes. Conclusiones: los antecedentes personales de pólipos colorrectales, el hábito de fumar, la diabetes mellitus tipo 2 y la obesidad fueron los factores de riesgo más encontrados. La forma de presentación más frecuente fue la enterorragia, seguida por la oclusión intestinal y las regiones del colon más afectadas fueron la descendente y la ascendente, respectivamente. El diagnóstico histológico fue en el mayor de los casos un adenocarcinoma. Existe una mayor frecuencia del diagnóstico en etapas avanzadas de la enfermedad

Introduction: Colorectal cancer represents the third in incidence in both sexes worldwide. For this reason, it is essential to carry out epidemiological studies of it. Objective: To characterize clinically, endoscopically and histologically colorectal cancer in patients treated at the Surgical Medical Research Center, Cuba. Methods: An observational, descriptive, and retrospective study of 52 patients (31 men and 21 women) with colorectal cancer diagnosed between 2012 and 2014 was carried out. Data from clinical histories, endoscopic imaging, and pathological studies were collected. The average age was 66.7 years Results: The antecedent and presence of polyps in the colon predominated with 55.8%. Enterorrhagia occurred in 38.5% of patients, intestinal occlusion, and abdominal pain in 17.3%. During the colonoscopy, 47.7% of patients were found with an ulcerated lesion, and the most compromised place was the descending colon (38.5%). Adenocarcinoma was found in 90.4% of patients. Conclusions: Personal history of colorectal polyps, smoking, type 2 diabetes mellitus, and obesity were the most common risk factors. The most common form of presentation was enterorrhagia, followed by intestinal occlusion, and the most affected regions of the colon were descending and ascending. The histological diagnosis was, in most cases, an adenocarcinoma. There was a higher frequency of diagnosis in advanced stages of the disease

Guest-host complexes of 1-iodochlordecone and ß-1-iodo-pentachlorocyclohexane with cyclodextrins as radiotracers of organochlorine pesticides in polluted water.

The chlordecone (CLD) and the ß-hexachlorocyclohexane (ß-HCH) are persistent organic pollutants with a great environmental stability that cause severe affectations to health. The concentration of these pesticides in the environment is low, which represent a problem for their determination, even for the modern analytical methods. The labeling of these compounds with an iodine radioisotope for their use as radiotracers is a potential solution to this problem. The present work studies the interaction of 1-iodochlordecone (I-CLD) and ß-1-iodo-pentachlorocyclohexane (I-ß-HCH) with cyclodextrins (CDs), during the formation of molecular inclusion complexes pesticide@CDs. The methodology of multiple minima hypersurfaces, quantic calculations based on density functional theory and a topologic study of electronic density were used to corroborate the stability of I-CLD@CDs and I-ß-HCH@CDs complexes. Three main types of guest-host complexes in relation to the occlusion grade were observed: with total occlusion, with partial occlusion and external interaction without occlusion. The more stable complexes are obtained when the γ-CD is the host molecule. The formed complexes with radiolabelled pollutants are analogous with the ones reported in previous works. These results confirm the utility of these complexes for the removal of organochlorine pesticides from polluted water and, also, demonstrate the possibility of using the I-CLD and the I-ß-HCH as possible radiotracers for these pollutants in further studies with environmental proposes.

Improving degradation of paracetamol by integrating gamma radiation and Fenton processes.

Degradation of paracetamol (N-(4-hydroxiphenyl)acetamide) in aqueous solution by gamma radiation, gamma radiation/H2O2 and gamma radiation/Fenton processes was studied. Parameters affecting the radiolysis of paracetamol such as radiation dose, initial concentration of pollutant, pH and initial oxidant concentration were investigated. Gamma radiation was performed using a (60)Co source irradiator. Paracetamol degradation and mineralization increased with increasing absorbed radiation dose, but decreased with increasing initial concentration of the drug in aqueous solution. The addition of H2O2 resulted in an increased effect on irradiation-driven paracetamol degradation in comparison with the performance of the irradiation-driven process alone: paracetamol removal increased from 48.9% in the absence of H2O2 to 95.2% for H2O2 concentration of 41.7 mmol/L. However, the best results were obtained with gamma radiation/Fenton process with 100% of the drug removal at 5 kGy, for optimal H2O2 and Fe(2+) concentrations at 13.9 and 2.3 mmol/L, respectively, with a high mineralization of 63.7%. These results suggest gamma radiation/H2O2 and gamma radiation/Fenton processes as promising methods for paracetamol degradation in polluted wastewaters.

Interacción de la 1-yodoclordecona como radiotrazador, con el grupo carboxilato en carbón activado / Interaction of 1-iodochlordecone, as radioactive tracer, with the carboxylate group on activated carbon

La clordecona es un compuesto organoclorado sintético, empleado como insecticida agrícola y clasificado como contaminante orgánico persistente de aguas y suelos por la Convención de Estocolmo. El uso de carbones activados es una metodología muy popular para la purificación de aguas contaminadas con contaminantes orgánicos persistentes. La clordecona marcada con yodo radiactivo (1-yodoclordecona) puede ser un radiotrazador adecuado para estudios de adsorción, de disponibilidad medioambiental y biodistribución de la clordecona. La selección del carbón activado más adecuado para la adsorción de clordecona requiere evaluar la eficiencia de una gran cantidad de los mismos, de manera empírica, lo que aumenta los costos de investigación. En el presente trabajo, un modelo simplificado de carbón activado con siete anillos aromáticos (coroneno) y un grupo funcional en el borde (carboxilato) se utilizó para evaluar in silico la influencia de este grupo superficial en la adsorción de la clordecona y la 1-yodoclordecona, bajo condiciones neutras de pH. Para ello se empleó la metodología de Hipersuperficie de Múltiples Mínimos con el hamiltoniano semiempírico PM7. Los resultados obtenidos muestran que para el carboxilato en medio neutro existen asociaciones significativas que sugieren quimisorción de la clordecona en el carbón activado. La 1-yodoclordecona se comporta de manera similar a la clordecona en su interacción con el carboxilato, por lo que constituye un buen candidato a radiotrazador para estudios experimentales.

Chlordecone is a synthetic organo chlorinated compound that has been used as pesticide. It has been identified and listed as persistent organic pollutant by the Stockholm Convention. The use of activated carbon filters is one of the most widely popular solutions for water decontamination. The chlordecone labeled with radioactive iodine (1-iodochordecone) is a potential radioactive tracer for studying adsorption, environmental availability and bio-distribution of chlordecone. The selection of the best suited activation carbon for this type of contaminants is mainly an empiric process, increasing the costs of research. A simplified activation carbon model, consisting of a seven ring graphene sheet with a functional group (carboxylate) was used to assess the interaction of chlordecone and 1-iodochlordecone with this surface group under neutral pH conditions over the adsorption process. The Multiple Minima Hypersurface methodology with the semiempirical Hamiltonian PM7 was used. The results indicate that for carboxylate, in neutral conditions, significant associations appear which suggest chemisorption in activated carbon. No significant differences were observed for the interactions of chlordecone and 1-iodochlordecone with carboxylate, making 1-iodochlordecone a good candidate as a radioactive tracer in medical research.

Calidad de vidaeen un grupo de mujeres Cubanas con cancer de mama / Quality of life in cuban patients with breast cancer

Se estudió un grupo de 16 pacientes cubanas, sometidas a cirugía y tratamiento por cáncer de mama con sobrevida mayor al año para evaluar el impacto del diagnóstico, la cirugía y el tratamiento concomitante en su calidad de vida. La calidad de vida del grupo en estudio es similar a la de grupos de referencia y a la de otras pacientes con cáncer de mama con más de un año de sobrevida, con un mejor funcionamiento físico. La evaluación de los exponentes del estado emocional, tales como nerviosismo, preocupación, irritabilidad y depresión, demostró que la evaluación de la calidad de la escala emocional ofrece valores significativamente inferiores a grupos normativos de otros países, pero se corresponde con el reportado para mujeres con cáncer de mama con igual tiempo de sobrevida e igual al valor obtenido para pacientes con cáncer en tratamiento y menos de un año de sobrevida.

A group of sixteen Cuban patients with breast cancer submitted to different surgery procedures and conventional oncological treatment with survival of one year and more was studied to evaluate the impact of diagnosis, surgery and concomitant treatment on quality-of life (QoL). The QoL of studied group was similar to that of reported for normative groups and to the others women with breast cancer, been the physical functioning of our group significantly better. The evaluation of emotional elements as nervousness, irritability and depression shows lower values of emotional functioning scale when compare with normative groups of other countries. However, the emotional functioning of studied group corresponds with the reported values for patients with survival of less than one year, one year and more.

Filtracion del vacio del Lobenzarit / Lobenzarit in vacuo filtration

Se estudio la filtracion del lobenzaria a presion cosntante con el empleo de polipropileno como material filtrante. Se determinaron la resistencia de la torta y del material filtrante, asi como la compresibilidad del lobenzarit durante la filtracion. Los resultados muestran que las particulas del solido se deforman considerablemente bajo la influencia de la presion