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The sulfonylurea herbicide family has been extensively studied using computational techniques. The most stable conformer structures of the 34 molecules analyzed in gaseous, aqueous, and octanol phases have been determined. The study employed CREST conformational search methods along with the CENSO script to explore all possible conformational structures. Additional evaluations conducted at the B3LYP-D3/6-311+G(d,p) level have enabled the identification of intramolecular stability patterns across the various compounds. It has been discovered that stability is primarily determined by two factors: intramolecular hydrogen bonding involving an NH group adjacent to the sulfonyl group with either N donors or the nearby carbonyl group and potential π-π interactions between the aromatic rings of the molecules. These have been characterized through QTAIM and NCI population analyses. Furthermore, with the goal of developing predictive models for the physicochemical properties of pesticides that include the sulfonylurea family, a statistical analysis among the different properties of the studied molecules has been conducted. Significant correlations have been found between various properties, predicting a promising future for the prediction of characteristics that could assist laboratories in selecting among different pesticides.
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Background and Objectives: High-grade malignant neuroendocrine tumors (G3 NETs) and neuroendocrine carcinomas (NECs) are characterized by rapid proliferation, high metastatic capacity, and strong expression of somatostatin receptors (SSTRs). We aimed to analyze the presence of SSTRs in NET G3 and NEC, and to correlate their expression with the use of octreotide and pasireotide. Materials and Methods: For this purpose, we first performed a retrospective study of G3 NET and NEC patients, which included the determination of SSTR expression and response to octreotide treatment. Second, we selected the H69 small cell lung cancer cell line to determine the effect of octreotide and pasireotide. Results: Our results showed the traditional somatostatin analog (SSA) octreotide was ineffective in patients with NET G3 and NEC. On the other hand, RT-qPCR showed a high expression of SSTR2 and SSTR5 in H69 cells. Interestingly, while octreotide did not modify H69 cell proliferation, a strong inhibition of proliferation was detected with the use of pasireotide. Conclusions: In view of these results, a clinical trial in NET G3 and NEC patients using pasireotide is necessary to determine the usefulness of this drug in improving patient treatment.
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Tumores Neuroendocrinos , Octreótido , Receptores de Somatostatina , Somatostatina , Humanos , Octreótido/uso terapéutico , Octreótido/farmacología , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Somatostatina/farmacología , Tumores Neuroendocrinos/tratamiento farmacológico , Receptores de Somatostatina/análisis , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Adulto , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
Plants provide a wide array of compounds that can be explored for potential anticancer properties. Siphonochilone, a furanoterpene that represents one of the main components of the African plant Siphonochilus aethiopicus, shows numerous health benefits. However, to date, its antiproliferative properties have not been tested. The aim of this study was to analyze the cytotoxic effects of siphonochilone on a panel of cancer cell lines and its underlying mechanism of action. Our results demonstrated that siphonochilone exhibited significant cytotoxic effects on pancreatic, breast, lung, colon, and liver cancer cell lines showing a IC50 ranging from 22 to 124 µM at 72 h of treatment and highlighting its cytotoxic effect against MCF7 and PANC1 breast and pancreas cancer cell lines (22.03 and 39.03 µM, respectively). Cell death in these tumor lines was mediated by apoptosis by the mitochondrial pathway, as evidenced by siphonochilone-induced depolarization of the mitochondrial membrane potential. In addition, siphonochilone treatment involves the generation of reactive oxygen species that may contribute to apoptosis induction. In this work, we described for the first time the cytotoxic properties of siphonochilone and provided data about the molecular processes of cell death. Although future studies will be necessary, our results support the interest in this molecule in relation to their clinical application in cancer, and especially in breast and pancreatic cancer.
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Apoptosis , Potencial de la Membrana Mitocondrial , Especies Reactivas de Oxígeno , Humanos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Zingiber officinale/química , Supervivencia Celular/efectos de los fármacosRESUMEN
Aberrant attentional salience has been implicated in the cannabis-psychosis association. Here, history and frequency of cannabis use were examined against changes in overshadowing (OS), a cue competition paradigm that involves salience processing. Additionally, we examined the association between OS and alternative measures of aberrant salience, as well as schizotypy, in a non-clinical adult sample. 280 participants completed an online geometry learning-based OS task, while a subset (N = 149) also completed the Salience Attribution Task (SAT) measure of aberrant salience. All completed the Schizotypal Personality Questionnaire (SPQ), Aberrant Salience Inventory (ASI), and the modified Cannabis Experience Questionnaire (CEQmv). Differences across OS and SAT performance stages and between cannabis use groups were assessed using mixed ANOVAs. Multiple regression and correlational analyses assessed the relationships between OS and SAT task metrics and SPQ and ASI subscale scores. Current cannabis users had significantly lower OS scores during the testing phase relative to those who do not use cannabis, at medium effect sizes. Schizotypy or ASI scores did not mediate this relationship. In the SAT, current cannabis users presented significantly higher implicit aberrant salience relative to non-users. Scores in the first training phase of the OS task significantly predicted higher explicit aberrant and adaptive salience scores in the SAT. These data indicate an association between regular cannabis use and abnormalities in cue competition effects in a healthy adult sample. Comparisons of OS and SAT cast new light on putative overlapping mechanisms underlying performance across different measures of salience.
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A new eusdesmane sesquiterpenoid, characterized as 3,5,8a-trimethyl-8-oxo-4,4a,5,6,7,8,8a,9-octahydronaphtho[2,3-b]furan-5-yl acetate (1), has been isolated from the rhizomes of the South African variety of wild ginger (Siphonochilus aethiopicus (Schweinf) B. L. Burtt). The compound was obtained by silica gel column chromatography. Its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass-spectrometric (MS) analyses, including 1D-, 2D-NMR, and HR-LCMS. We also investigated the cytotoxic effect of 1 on a panel of cancer cell lines, human breast, pancreas, lung, colon, and central nervous system cancer lines. The data are not encouraging since its antitumor effect is poor. Nonetheless, the discovery of new molecules may provide a source of new compounds with important biological effects applicable to the field of medicine.
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Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.
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Antineoplásicos , Productos Biológicos , Neoplasias Pulmonares , Poríferos , Animales , Poríferos/química , Productos Biológicos/farmacología , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Organismos AcuáticosRESUMEN
The prevalence of obesity increases alarmingly every year mostly due to external factors such as high-fat and high-refined sugar intake associated with a sedentary lifestyle. It triggers metabolic disorders such as insulin resistance, hyperlipemia, non-alcoholic fatty liver disease, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. The aim of this study was to evaluate the beneficial effects of a combined intervention with caloric restriction, nutraceutical intake, and a mixed training protocol on oxidative stress, inflammation, and gut dysbiosis derived from the development of obesity in a C57BL6/J mouse experimental model of diet-induced obesity (4.6 Kcal/g diet, 45% Kcal as fat, and 20% fructose in the drinking fluid). The nutraceutical was formulated with ethanolic extracts of Argania spinosa pulp (10%) and Camelina sativa seeds (10%) and with protein hydrolysates from Psoralea corylifolia seeds (40%) and Spirodela polyrhiza whole plants (40%). The combination of nutraceutical and exercise decreased the animals' body weights and inflammatory markers (TNFα, IL-6, and resistin) in plasma, while increasing gene expression of cat, sod2, gsta2, and nqo1 in the liver. Obese animals showed lower ß-diversity of microbiota and a higher Firmicutes/Bacteroidetes ratio vs. normocaloric controls that were reversed by all interventions implemented. Dietary inclusion of a nutraceutical with high antioxidant potential combined with an exercise protocol can be beneficial for bodyweight control and improvement of metabolic status in patients undergoing obesity treatment.
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Purpose: The lack of specificity of conventional chemotherapy is one of the main difficulties to be solved in cancer therapy. Biomimetic magnetoliposomes are successful chemotherapy controlled-release systems, hyperthermia, and active targeting agents by functionalization of their surface with monoclonal antibodies. The membrane receptor Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) stands out as colorectal cancer (CRC) biomarker and appears to be related to treatment resistance and the development of metastasis. The aim of this study was to assess the effectiveness and safety of LGR5-targeted biomimetic magnetoliposomes loaded with oxaliplatin (OXA) or 5-fluorouracil (5-FU) in the selective treatment of CRC and their possible application in hyperthermia. Methods: Synthesis, characterization and determination of heating capacity of magnetoliposomes transporting OXA or 5-FU (with and without LGR5 functionalization) were conducted. In vitro antitumoral activity was assayed in multiple colorectal cell lines at different times of exposition. In addition to this, cell internalization was studied by Prussian Blue staining, flow cytometry and fluorescence microscopy. In vivo acute toxicity of magnetoliposomes was performed to evaluate iron-related toxicity. Results: OXA and 5-FU loaded magnetoliposomes functionalized with LGR5 antibody showed higher cellular uptake than non-targeted nanoformulation with a reduction of the percentage of proliferation in colon cancer cell lines up to 3.2-fold of the IC50 value compared to that of free drug. The differences between non-targeted and targeted nanoformulations were more evident after short exposure times (4 and 8 hours). Interestingly, assays in the MC38 transduced cells with reduced LGR5 expression (MC38-L(-)), showed lower cell internalization of LGR5-targeted magnetoliposomes compared to non-transduced MC38 cell line. In addition, magnetoliposomes showed an in vitro favorable heating response under magnetic excitation and great iron-related biocompatibility data in vivo. Conclusion: Drug-loaded magnetoliposomes functionalized with anti-LGR5 antibodies could be a promising CRC treatment strategy for LGR5+ targeted chemotherapy, magnetic hyperthermia, and both in combination.
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Neoplasias del Colon , Neoplasias Colorrectales , Hipertermia Inducida , Humanos , Biomimética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Fluorouracilo/uso terapéutico , Oxaliplatino/uso terapéutico , Hierro , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patologíaRESUMEN
The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.
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Neoplasias Experimentales , Animales , Embrión de Pollo , Humanos , Bioensayo , Membrana Corioalantoides , Medicina de PrecisiónAsunto(s)
Disección , Vena Cava Inferior , Humanos , Vena Cava Inferior/cirugía , Espacio Retroperitoneal , AbdomenRESUMEN
BACKGROUND: Liposomal Doxorubicin (Doxil®) was one of the first nanoformulations approved for the treatment of solid tumors. Although there is already extensive experience in its use for different tumors, there is currently no grouped evidence of its therapeutic benefits in non-small cell lung cancer (NSCLC). A systematic review of the literature was performed on the therapeutic effectiveness and benefits of Liposomal Doxil® in NSCLC. METHODS: A total of 1022 articles were identified in publications up to 2020 (MEDLINE, Cochrane, Web of Science Core Collection and Scopus). After applying inclusion criteria, the number was restricted to 114, of which 48 assays, including in vitro (n=20) and in vivo (animals, n=35 and humans, n=6) studies, were selected. RESULTS: The maximum inhibitory concentration (IC50), tumor growth inhibition rate, response and survival rates were the main indices for evaluating the efficacy and effectiveness of Liposomal DOX. These have shown clear benefits both in vitro and in vivo, improving the IC50 of free DOX or untargeted liposomes, depending on their size, administration, or targeting. CONCLUSION: Doxil® significantly reduced cellular proliferation in vitro and improved survival in vivo in both experimental animals and NSCLC patients, demonstrating optimal safety and pharmacokinetic behavior indices. Although our systematic review supports its benefits for the treatment of NSCLC, additional clinical trials with larger sample sizes are necessary to obtain more precise clinical data on its activity and effects in humans.
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Antibióticos Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Doxorrubicina , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Humanos , Animales , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Polietilenglicoles/química , Proliferación Celular/efectos de los fármacos , LiposomasRESUMEN
Bielecki et al. Current Biology, 33, 4150-4159, (2023) described new behavioral and physiological paradigms to study associative learning and its neural basis in the Cnidaria Tripedalia cystophora. We discuss the relevance of these findings to further our understanding of the intertwined evolution of cognition and the nervous systems.
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Recently, the classical anatomy of the quadriceps femoris has been questioned after the publication of various morphological variations that differ from the classical description. Therefore, it is necessary to collect information to reach an agreement on its structure. For this, a systematic review was carried out using the Web of Science, Pubmed and ProQuest scientific databases, obtaining a total of 29 papers finally included in the systematic review after being subjected to inclusion and exclusion criteria. The results obtained showed an important and variable prevalence of new configurations described, such as additional heads in the rectus femoris, a different origin of the vastus intermedius, various portions of the vastus lateralis, or the involvement of the vastus medialis in the patellofemoral musculature. For this reason, understanding the anatomy of the quadriceps femoris is a matter that has not yet been fully resolved, with high variability among people that must be studied prior to the application of an invasive and/or surgical procedure.
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Lung cancer is the most commonly diagnosed cancer and the one that causes the most deaths worldwide, so there is a need for therapies that improve survival rates. Products derived from marine organisms are a source of novel and potent antitumor compounds, but they present the great obstacle of their obtaining from the natural environment and the problems associated with the synthesis and biological effects of chemical analogues. In this work, a Bengamide analogue (Bengamide II) was chemically synthesized and in vitro and in vivo studies were performed to determine its antitumor activity and mechanisms of action. It was shown to have potent antiproliferative activity in lung cancer lines in 2D and 3D models. In addition, Bengamide II-treated cells showed G2/M and G0/G1 cell cycle arrest, together with a decrease in the proliferation marker Ki67. As for the mechanism of action, the treatment was associated with increased LC3-II expression and production of acidic vesicles signaling autophagy. In addition, Bengamide II treatment was associated with caspase-3 activation and DNA fragmentation related to apoptosis. Furthermore, a reduction of VEGFA expression, related to angiogenesis, was also observed. In vivo studies showed that Bengamide II markedly reduced tumor volume and metastases increasing survival. Additionally, it revealed no systemic toxicity in in vivo models at the therapeutic doses used, which is essential for its future clinical use. Taken together, the chemically synthesized bengamide analogue Bengamide II, is a promising drug for lung cancer treatment showing relevant antitumor activity and significant safety.
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Antineoplásicos , Neoplasias Pulmonares , Humanos , Animales , Ratones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proliferación Celular , Línea Celular Tumoral , Transducción de Señal , ApoptosisRESUMEN
Among the most harmful tumors detected in the human body, such as breast, colon, brain or pancreas, breast (BC) and colorectal cancer (CRC) are the first and third most frequent cancer worldwide, respectively. The current existing chemotherapeutic treatments present serious side effects due to their intravenous administration can induce cytotoxicity in healthy cells. Thus, new treatment methods based on drug-loaded polymeric nanofibers (NFs) have gained significant potential for their use in localized cancer chemotherapy. Here, a deep in vitro comparative analysis between maslinic acid (MA) and a tyramine-maslinic acid (TMA) derivative is initially performed. This analysis includes a proliferation, and a cell cycle assay, and a genotoxicity, antiangiogenic and apoptosis study. Then, the TMA derivative has been incorporated into electrospun polymeric NFs obtaining an implantable dressing material with antitumor activity. Two types of patches containing TMA-loaded polymeric NFs of poly(caprolactone) (PCL), and a mixture of polylactic acid/poly(4-vinylpyridine) (PLA/PVP) were fabricated by the electrospinning technique. The characterization of the drug-loaded NFs showed an encapsulation capacity of 0.027 mg TMA/mg PCL and 0.024 mg TMA/mg PLA/PVP. Then, the cytotoxic activity of both polymeric systems was tested in CRC (T84), BC (MCF-7) and a no tumor (L929) cell lines exposed to TMA-loaded NFs and blank NFs for 48 h. Moreover, cell cycle assay, genotoxicity, angiogenesis and apoptosis tests were carried out to study the mechanism of action of TMA. Blank NFs showed no-toxicity in all cell lines tested and both drug-loaded NFs significantly reduced cell proliferation (relative proliferation of ≈44 % and ≈25 % respectively). Therefore, TMA was less genotoxic than maslinic acid (MA), and reduced VEGFA expression in MCF-7 cells (1.32 and 2.12-fold for MA and TMA respectively). These results showed that TMA-loaded NFs could constitute a promising biocompatible and biodegradable nanoplatform for the local treatment of solid tumors such as CRC or BC.
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Nanofibras , Neoplasias , Humanos , Preparaciones Farmacéuticas , Polímeros , PoliésteresRESUMEN
SUMMARY: Telocytes are a cell population described in 2011 with a multitude of functions such as tissue support, regulation of stem cell niches or intercellular signal transmission. However, there are no studies about their embryonic origin, their function in development, or their moment of appearance. The objective of this work is to try to answer these questions through histological and immunofluorescence studies with samples from the embryological collection of the Department of Anatomy of the University of Granada. In the results obtained, as demonstrated by immunofluorescence for CD34, the presence of these cells can be seen in the fourth week of embryonic development in the perinotochordal region. Its presence is evident from the sixth week of development in a multitude of organs such as the heart, skeletal muscle tissue and supporting tissue of various organs such as the kidney, brain or pericardium. Its function seems to be when the embryonic histological images are analyzed in an evolutionary way, to act as a scaffold or scaffold for the subsequent population by mature tissue elements. In conclusion, telocytes appear at a very early stage of embryonic development and would have a fundamental role in it as scaffolding and directors of organ and tissue growth.
Los telocitos son una población celular descrita en 2011 con multitud de funciones como el sostén tisular, la regulación de los nichos de células madre o la transmisión de señales intercelulares. Sin embargo, no existen estudios acerca del origen embrionario de los mismos, su función en el desarrollo ni su momento de aparición. El objetivo de este trabajo es tratar de responder a estos interrogantes mediante estudios histológicos y por inmunofluorescencia con muestras de la colección embriológica del Departamento de Anatomía de la Universidad de Granada. En los resultados se puede observar como se demuestra mediante inmunofluorescencia para CD34, la presencia de estas células en la cuarta semana del desarrollo embrionario en la región perinotocordal. Su presencia se evidencia a partir de la sexta semana del desarrollo en multitud de órganos como corazón, tejidos músculo esqueléticos y tejidos de sostén de diversos órganos como riñón, encéfalo o pericardio. Su función parece ser al ser analizadas las imágenes histológicas embrionarias de forma evolutiva, la de actuar como un andamiaje o scafold para el posterior poblamiento por elementos tisulares maduros. Como conclusión, los telocitos aparecen en un momento muy precoz del desarrollo embrionario y presentarían una función fundamental en el mismo como andamiajes y directores del crecimiento de los órganos y tejidos.
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Humanos , Telocitos/metabolismo , Telocitos/ultraestructura , Técnica del Anticuerpo Fluorescente , Antígenos CD34RESUMEN
Introduction: Pancreatic cancer (PC) shows a very poor response to current treatments. Development of drug resistance is one of the causes of the therapy failure, being PARP1 (poly ADP-ribose polymerase 1) a relevant protein in the resistance mechanism. In this work, we have functionalized calcium phosphate-based nanoparticles (NPs) with Olaparib (OLA, a PARP-1 inhibitor) in combination with ascorbic acid (AA), a pro-oxidative agent, to enhance their individual effects. Methods: Amorphous Calcium Phosphate (ACP) NPs were synthesized through a biomimetic approach and then functionalized with OLA and AA (NP-ACP-OLA-AA). After evaluation of the loading capacity and release kinetic, cytotoxicity, cell migration, immunofluorescence, and gene expression assays were performed using pancreatic tumor cell lines. In vivo studies were carried out on tumors derived from the PANC-1 line in NOD SCID gamma (NSG) mice. Results: NP-ACP-OLA-AA was loaded with 13%wt of OLA (75% loading efficiency) and 1% of AA, respectively. The resulting dual nanosystem exhibited a gradual release of OLA and AA, being the latter protected from degradation in solution. This ensured the simultaneous availability of OLA and AA for a longer period, at least, during the entire time of in vitro cell experiments (72 hours). In vitro studies indicated that NP-ACP-OLA-AA showed the best cytotoxic effect outperforming that of the free OLA and a higher genotoxicity and apoptosis-mediated cytotoxic effect in human pancreatic ductal adenocarcinoma cell line. Interestingly, the in vivo assays using immunosuppressed mice with PANC-1-induced tumors revealed that NP-ACP-OLA-AA produced a higher tumor volume reduction (59.1%) compared to free OLA (28.3%) and increased the mice survival. Conclusion: Calcium phosphate NPs, a highly biocompatible and biodegradable system, were an ideal vector for the OLA and AA co-treatment in PC, inducing significant therapeutic benefits relative to free OLA, including cytotoxicity, induction of apoptosis, inhibition of cell migration, tumor growth, and survival.
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Neoplasias Pancreáticas , Humanos , Animales , Ratones , Ratones SCID , Neoplasias Pancreáticas/tratamiento farmacológico , Ácido Ascórbico/farmacología , Neoplasias PancreáticasRESUMEN
Three experiments explored whether weakening temporal contiguity between auditory cues and an aversive outcome attenuated cue competition in an avoidance learning task with human participants. Overall, with strong temporal contiguity between auditory cues and the outcome during training (the offset of the predictive auditory signals concurred with the onset of the outcome), the target cue trained as part of a compound yielded less avoidance behaviour than the control cue trained alone, an instance of overshadowing. However, weakening temporal contiguity during training (inserting a 5-s trace) attenuated overshadowing, resulting in similar avoidance behaviour in response to the control and target cues. These results provide evidence that, as predicted by a recent modification of Pearce's configural theory, temporal contiguity is critical for determining cue competition.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical resection, but due to the delay in diagnosis, less than 20% of patients are eligible for surgery. Therefore, discovering diagnostic biomarkers for early detection is crucial for improving clinical outcomes. Metabolomics has become a powerful technology for biomarker discovery, and several metabolomic-based panels have been proposed for PDAC diagnosis, but these advances have not yet been translated into the clinic. Therefore, this review focused on summarizing metabolites identified for the early diagnosis of PDAC in the last five years. Bibliographic searches were performed in the PubMed, Scopus and WOS databases, using the terms "Biomarkers, Tumor", "Pancreatic Neoplasms", "Early Diagnosis", "Metabolomics" and "Lipidome" (January 2018-March 2023), and resulted in the selection of fourteen original studies that compared PDAC patients with subjects with other pancreatic diseases. These investigations showed amino acid and lipid metabolic pathways as the most commonly altered, reflecting their potential for biomarker research. Furthermore, other relevant metabolites such as glucose and lactate were detected in the pancreas tissue and body fluids from PDAC patients. Our results suggest that the use of metabolomics remains a robust approach to improve the early diagnosis of PDAC. However, these studies showed heterogeneity with respect to the metabolomics techniques used and further studies will be needed to validate the clinical utility of these biomarkers.
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Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.