From proteomic analysis to potential therapeutic targets: functional profile of two lung cancer cell lines, A549 and SW900, widely studied in pre-clinical research

Lung cancer is a serious health problem and the leading cause of cancer death worldwide. The standard use of cell lines as in vitro pre-clinical models to study the molecular mechanisms that drive tumorigenesis and access drug sensitivity/effectiveness is of undisputable importance. Label-free mass spectrometry and bioinformatics were employed to study the proteomic profiles of two representative lung cancer cell lines and to unravel the specific biological processes. Adenocarcinoma A549 cells were enriched in proteins related to cellular respiration, ubiquitination, apoptosis and response to drug/hypoxia/oxidative stress. In turn, squamous carcinoma SW900 cells were enriched in proteins related to translation, apoptosis, response to inorganic/organic substances and cytoskeleton organization. Several proteins with differential expression were related to cancer transformation, tumor resistance, proliferation, migration, invasion and metastasis. Combined analysis of proteome and interactome data highlighted key proteins and suggested that adenocarcinoma might be more prone to PI3K/Akt/mTOR and topoisomerase IIα inhibitors, and squamous carcinoma to Ck2 inhibitors. Moreover, ILF3 overexpression in adenocarcinoma, and PCNA and NEDD8 in squamous carcinoma shows them as promising candidates for therapeutic purposes. This study highlights the functional proteomic differences of two main subtypes of lung cancer models and hints several targeted therapies that might assist in this type of cancer.publishe

Opportunities for the Development of Neuroimmune Therapies in Addiction

Studies have implicated neuroinflammatory processes in the pathophysiology of various psychiatric conditions, including addictive disorders. Neuroimmune signaling represents an important and relatively poorly understood biological process in drug addiction. The objective of this review is to update the field on recent developments in neuroimmune therapies for addiction. First, we review studies of neuroinflammation in relation to alcohol and methamphetamine dependence followed by a section on neuroinflammation and accompanying neurocognitive dysfunction in HIV infection and concomitant substance abuse. Second, we provide a review of pharmacotherapies with neuroimmune properties and their potential development for the treatment of addictions. Pharmacotherapies covered in this review include ibudilast, minocycline, doxycycline, topiramate, indomethacin, rolipram, anakinra (IL-1Ra), peroxisome proliferator-activated receptor agonists, naltrexone, and naloxone. Lastly, summary and future directions are provided with recommendations for how to efficiently translate preclinical findings into clinical studies that can ultimately lead to novel and more effective pharmacotherapies for addiction

Toll-like receptor signaling and stages of addiction

Athina Markou and her colleagues discovered persistent changes in adult behavior following adolescent exposure to ethanol or nicotine consistent with increased risk for developing addiction. Building on Dr. Markou's important work and that of others in the field, researchers at the Bowles Center for Alcohol Studies have found that persistent changes in behavior following adolescent stress or alcohol exposure may be linked to induction of immune signaling in brain. This study aims to illuminate the critical interrelationship of the innate immune system (e.g., toll-like receptors [TLRs], high-mobility group box 1 [HMGB1]) in the neurobiology of addiction. This study reviews the relevant research regarding the relationship between the innate immune system and addiction. Emerging evidence indicates that TLRs in brain, particularly those on microglia, respond to endogenous innate immune agonists such as HMGB1 and microRNAs (miRNAs). Multiple TLRs, HMGB1, and miRNAs are induced in the brain by stress, alcohol, and other drugs of abuse and are increased in the postmortem human alcoholic brain. Enhanced TLR-innate immune signaling in brain leads to epigenetic modifications, alterations in synaptic plasticity, and loss of neuronal cell populations, which contribute to cognitive and emotive dysfunctions. Addiction involves progressive stages of drug binges and intoxication, withdrawal-negative affect, and ultimately compulsive drug use and abuse. Toll-like receptor signaling within cortical-limbic circuits is modified by alcohol and stress in a manner consistent with promoting progression through the stages of addiction

Evaluación financiera de plan de negocio industrial de peces amazónicos de “Acuicultura Ucayali” - ubicado en la ciudad de Pucallpa – Ucayali – Perú

Desarrolla un plan de negocios ante una necesidad actual, el creciente aumento de la población en ciudades principales e intermedias, aunado a la depredación desmedida por nuestros recursos hidrobiológicos, entre ellos las diferentes variedades de peces amazónicos (Gamitana, Paco, Corvina, Doncella, Paiche, etc), ha ocasionado que en los últimos 15 años el desembarque en toneladas de productos pesqueros sea menor cada año (más de 10,000 toneladas en 1997 ha poco más de 3000 toneladas en el 2012). Esta disminución entre otras cosas ha generado que estas variedades de producto estén más escasas y siempre su precio al consumidor final se esté incrementado. Se presenta como una oportunidad importante que permitirá a la empresa Acuicultura Ucayali, posicionarse rápidamente como un proveedor importante dentro de esta actividad, hay factores que de alguna manera se convierten en aliados para un desarrollo efectivo de la empresa, el primero que la competencia directa por el lado de los alevines corresponde a instituciones del estado que su capacidad de respuesta y flexibilidad es una ventaja a favor de nuestro interés, por parte de nuestro segundo producto existe una mayor competencia con producción de captura pero no se encuentra articulada como un producto sólida que pueda sostener una oferta.. El Plan de Negocio en los primeros 10 años es bastante conservador, con una inversión inicial de alrededor de 5 millones de los cuales el 62 % es patrimonio y el saldo corresponde a endeudamiento. En base al análisis realizado en el presente plan se obtiene una TIR de 20.24% y un VAN de 3`945,521 millones, lo que hace que el proyecto cuente con una aceptable proyección.Tesi