Testicular fusocellular rhabdomyosarcoma as a metastasis of elbow sclerosing rhabdomyosarcoma: A clinicopathologic, immunohistochemical and molecular study of one case

Sclerosing rhabdomyosarcoma (SRMS) is an infrequent variant of rhabdomyosarcoma characterized by extensive intercellular hyaline fibrosis. We report the case of a 37 year-old male with a 9 × 6 cm SRMS on the right elbow. Histologically, the tumor showed an abundant extracellular hyaline matrix with extratumoral vascular emboli and microscopic foci of fusocellular embryonal rhabdomyosarcoma (FRMS) separated by a fibrotic band from the sclerosing areas. One year later the patient presented with a right intratesticular tumor of 1.2 × 0.8 cm, which was reported as pure FRMS. Immunohistochemically, SRMS was positive only for MyoD1 and Vimentin and negative for Myogenin and Desmin. Both the elbow emboli with the extratumoral foci of FRMS and the intratesticular tumor were positive for Myogenin, MyoD1, Vimentin and Desmin. Using fluorescent in situ hybridization (FISH), the SRMS and the FRMS tumor cells of the elbow and the FRMS tumor cells of the testis were found to be negative for FOXO1A translocation in chromosome 13. PCR chimeric transcriptional products PAX3-FKHR and PAX7-FKHR were not found. Six months following testicular resection, the patient died of multiple metastases in the mediastinum, lung and right thigh

Phytochemical and crystallographic studies of Azara dentata extracts and its cytotoxic effects on human breast cancer cell, MCF-7

Azara dentata Ruiz & Pav. also called “Corcolen” is an endemic shrub of Chile. The honey produced in areas with abundance of Azara dentata is highly appreciate by its polyphenols. In the present work, we isolated and identified for the first time the phytochemical components of Azara dentata and its cytotoxic effects were analyzed on cancer cells together with its antimicrobial activity. The results showed that palmitic acid methyl ester, linolenic acid methyl ester, α-tocopherol and β-sitosterol are the main non-polar constituents of the plant, while the compounds AD-3 (3-phenylisocoumarin, 0.0001% yield) and AD-4 (methyl 2-phenacyl-benzoate, 0.00039% yield) were isolated by column chromatography with n-hexane/EtOAc (3:2 v/v) and their structures were determined using NMR analysis. In addition, the structure of AD-4 was complemented by a single crystal x-ray structural determination. Azara dentata showed moderate antibacterial activity against S. aureus and S. epidermidis with a MIC of 5.0 and 10 mg/mL respectively. The cytotoxic activity of Azara dentata against MCF-7 cancer cells showed an IC50 of 15.63 µg/mL, this is a promissory value for the deeper study of its metabolites in cancer models.Fil: Paz, Cristian. Universidad de La Frontera; ChileFil: González Chavarría, Iván. Universidad de Concepción; ChileFil: Freire Espeleta, Eleonora. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigaciones y Aplicaciones no Nucleares. Gerencia de Física (Centro Atómico Constituyentes); Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortiz, Leandro. Universidad Austral de Chile; ChileFil: Karpiński, Tomasz M.. Poznan University Of Medical Sciences; PoloniaFil: Duprat, Felix. Universidad de Concepción; ChileFil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigaciones y Aplicaciones no Nucleares. Gerencia de Física (Centro Atómico Constituyentes); Argentin

Effective nephroprotection against acute kidney injury with a star-shaped polyglutamate-curcuminoid conjugate

The lack of efective pharmacological treatments for acute kidney injury (AKI) remains a signifcant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (StPGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and infammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGAbased therapeutics may improve nephroprotective properties of current AKI treatmentsTis work was supported by grants from the Instituto de Salud Carlos III, FEDER funds: PI16/02057, PI16/01900, PI18/01133, PI19/00815, ISCIII RETIC REDINREN RD16/0009; Sociedad Española de Nefrología; FRIAT; Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM; ERA-PerMed-JTC2018 (AC18/00071; DTS18/00032); Spanish Ministry of Economy and Competitiveness (Grant numbers SAF2013-44848-R, SAF2016-80427-R). Partly co-funded by FEDER (PO FEDER Valencian Community - 2014–2020

Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling

The introduction of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus greatly reduced the rate of allograft rejection, although their chronic use is marred by a range of side effects, among them vascular toxicity. In transplant patients, it is proved that innate immunity promotes vascular injury triggered by ischemia-reperfusion damage, atherosclerosis and hypertension. We hypothesized that activation of the innate immunity and inflammation may contribute to CNI toxicity, therefore we investigated whether TLR4 mediates toxic responses of CNIs in the vasculature. Cyclosporine and tacrolimus increased the production of proinflammatory cytokines and endothelial activation markers in cultured murine endothelial and vascular smooth muscle cells as well as in ex vivo cultures of murine aortas. CNI-induced proinflammatory events were prevented by pharmacological inhibition of TLR4. Moreover, CNIs were unable to induce inflammation and endothelial activation in aortas from TLR4−/− mice. CNI-induced cytokine and adhesion molecules synthesis in endothelial cells occurred even in the absence of calcineurin, although its expression was required for maximal effect through upregulation of TLR4 signaling. CNI-induced TLR4 activity increased O2 −/ROS production and NF-κB-regulated synthesis of proinflammatory factors in cultured as well as aortic endothelial and VSMCs. These data provide new insight into the mechanisms associated with CNI vascular inflammationThis work was supported by grants from the Instituto de Salud Carlos III (Ministerio de Economía Competitividad, Gobierno de España): FEDER funds ISCIII RETIC REDINREN RD12/0021, PI11/02242, PI13/00047, PI14/0041, PI14/00386, PI15/01460; Comunidad de Madrid (CIFRA S2010/BMD-2378); Sociedad Española de Nefrología. Salary support: RR-D: CIFRA; CO-S: Fundación Conchita Rábago de Jiménez Díaz; CG-G and RRR-D: REDINREN; AO: Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM); JE and MRO: Universidad Autónoma de Madrid; AMR: Contrato Miguel Serve (ISCIII

SIMULACIÓN COMPUTACIONAL DEL PROCESO GLOBAL DE BIOTRANSFORMACIÓN DE FENOL EN AGUAS RESIDUALES INDUSTRIALES DE REFINERÍAS DE PETRÓLEO

RESUMENEl presente trabajo consiste en el planteamiento y desarrollo de un modelo matemático del proceso en continuo de biodegradación de fenol que toma parte en el tratamiento de aguas residuales industriales de las principales refinerías de la empresa ECOPETROL. El agua residual con compuestos fenólicos provenientes de los diferentes efluentes de procesos, es sometida a un proceso de tratamiento biológico utilizando un consorcio bacteriano altamente especializado.  En una primera fase se evaluaron cada una de las variables del bio-proceso y se planteó un modelo matemático global que describe el proceso a partir de las variables más importantes involucradas en el sistema de biodegradación del fenol. Para la cinética de crecimiento celular se utilizó la ecuación de Haldane, se determinaron los parámetros cinéticos a partir de pruebas experimentales a escala laboratorio y piloto y se evaluaron los efectos de condiciones de pH, suministro de oxígeno y componentes inhibitorios del bio-proceso. En el presente trabajo, el conjunto de ecuaciones diferenciales ordinarias simultáneas obtenidas a partir del planteamiento del modelo matemático, fue resuelto mediante un método numérico (Runge-Kutta de cuarto orden) utilizando Matlab 6.5. El desarrollo del modelo matemático y el diseño y puesta en marcha de una aplicación software, como herramienta metodológica, logró a partir de las interacciones virtuales con el bio-proceso, una mayor comprensión del sistema de biotransformación de fenol y la identificación de sus variables más relevantes. Palabras clave: Aguas residuales industriales, tratamiento biológico, modelo matemático y simulación. ABSTRACTThe present work is to approach and develop a mathematical model of the continuous process of biodegradation of phenol which takes part in the treatment of industrial waste water of the main refineries of the company ECOPETROL. The waste water with phenolic compounds derived from the effluents of different processes, is undergoing a process of biological treatment using a highly specialized bacterial consortium. In a first phase evaluated each of the variables in the bio-process and posed a mathematical model that describes the overall process from the most important variables involved in the biodegradation of phenol. For the kinetics of cell growth using the equation of Haldane, the kinetic parameters were determined from experimental tests on laboratory scale and pilot and assessed the effects of pH conditions, oxygen supply and inhibitory components of the bio-process. In this work, the set of ordinary differential equations simultaneously obtained from the approach of the mathematical model was solved using a numerical method (Runge-Kutta fourth-order) using Matlab 6.5. The development of the mathematical model and the design and implementation of a software application, such as methodological tool, managed from virtual interactions with the bio-process, a greater understanding of the biotransformation of phenol and identification of its variables relevant.Keywords: industrial waste water, biological, mathematical modeling and simulation

SIMULACIÓN COMPUTACIONAL DEL PROCESO GLOBAL DE BIOTRANSFORMACIÓN DE FENOL EN AGUAS RESIDUALES INDUSTRIALES DE REFINERÍAS DE PETRÓLEO

RESUMENEl presente trabajo consiste en el planteamiento y desarrollo de un modelo matemático del proceso en continuo de biodegradación de fenol que toma parte en el tratamiento de aguas residuales industriales de las principales refinerías de la empresa ECOPETROL. El agua residual con compuestos fenólicos provenientes de los diferentes efluentes de procesos, es sometida a un proceso de tratamiento biológico utilizando un consorcio bacteriano altamente especializado.  En una primera fase se evaluaron cada una de las variables del bio-proceso y se planteó un modelo matemático global que describe el proceso a partir de las variables más importantes involucradas en el sistema de biodegradación del fenol. Para la cinética de crecimiento celular se utilizó la ecuación de Haldane, se determinaron los parámetros cinéticos a partir de pruebas experimentales a escala laboratorio y piloto y se evaluaron los efectos de condiciones de pH, suministro de oxígeno y componentes inhibitorios del bio-proceso. En el presente trabajo, el conjunto de ecuaciones diferenciales ordinarias simultáneas obtenidas a partir del planteamiento del modelo matemático, fue resuelto mediante un método numérico (Runge-Kutta de cuarto orden) utilizando Matlab 6.5. El desarrollo del modelo matemático y el diseño y puesta en marcha de una aplicación software, como herramienta metodológica, logró a partir de las interacciones virtuales con el bio-proceso, una mayor comprensión del sistema de biotransformación de fenol y la identificación de sus variables más relevantes. Palabras clave: Aguas residuales industriales, tratamiento biológico, modelo matemático y simulación. ABSTRACTThe present work is to approach and develop a mathematical model of the continuous process of biodegradation of phenol which takes part in the treatment of industrial waste water of the main refineries of the company ECOPETROL. The waste water with phenolic compounds derived from the effluents of different processes, is undergoing a process of biological treatment using a highly specialized bacterial consortium. In a first phase evaluated each of the variables in the bio-process and posed a mathematical model that describes the overall process from the most important variables involved in the biodegradation of phenol. For the kinetics of cell growth using the equation of Haldane, the kinetic parameters were determined from experimental tests on laboratory scale and pilot and assessed the effects of pH conditions, oxygen supply and inhibitory components of the bio-process. In this work, the set of ordinary differential equations simultaneously obtained from the approach of the mathematical model was solved using a numerical method (Runge-Kutta fourth-order) using Matlab 6.5. The development of the mathematical model and the design and implementation of a software application, such as methodological tool, managed from virtual interactions with the bio-process, a greater understanding of the biotransformation of phenol and identification of its variables relevant.Keywords: industrial waste water, biological, mathematical modeling and simulation

Cirurgia oncològica digestiva: càncer d’estómac (2005-2016)

Cirurgia oncològica digestiva; Càncer d'estómac; HospitalitzacióCirugía oncológica digestiva; Cáncer de estómago; HospitalizaciónDigestive oncology surgery; Stomach cancer; HospitalizationEl càncer d'estómac ocupa actualment el segon lloc en freqüència entre els càncers de l'aparell digestiu. Tot i que la seva incidència és molt variable entre països, en els últims anys ha baixat en els països del primer món. El tractament quirúrgic segueix sent la principal opció a considerar per a tots els pacients amb càncer d'estómac potencialment curables. L'objectiu de l'atles és identificar i descriure la variabilitat en les hospitalitzacions per cirurgia de càncer d'estómac en homes i dones majors de 35 anys pel període de 2005 a 2016

Cirurgia oncològica digestiva: càncer de pàncrees (2005-2016)

Cirurgia oncològica digestiva; Càncer de pàncrees; HospitalitzacióCirugía oncológica digestiva; Cáncer de pàncreas; HospitalizaciónDigestive oncology surgery; Cancer of pancreas; HospitalizationEl càncer de pàncrees és un càncer difícil de detectar i diagnosticar. Alhora, la gravetat de la malaltia i l’absència d’un tractament efectiu fan que continuï sent actualment un dels processos neoplàsics de pitjor pronòstic. La cirurgia és l’única alternativa terapèutica actual potencialment curativa, encara que només per a pocs pacients. No es disposa de gaire informació sobre el maneig del pacient a la pràctica clínica habitual, i de com aquest influeix en els resultats obtinguts. Al 2012 es produeix la reordenació de l’atenció oncològica d’alta especialització (Instrucció 01/2012 del Catsalut) i resulta de gran interès veure l’impacte en l’accés a aquest tipus d’intervencions i en els resultats en termes de mortalitat intrahospitalària i posthospitalària (fins a 90 dies post-alta)

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure

whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. Methods: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. Results: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. Conclusion: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function

In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively.Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19.Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics.Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at