A peculiar Roman wheel-turned cup makes in red clay, of indigenous tradition, from Herrera de Pisuerga (Palencia, Spain)

En este artículo vamos a estudiar un tipo de copa de gran esbeltez al disponer de un elevado fuste hueco apoyado sobre un amplio pie acampanado, que está fabricada en cerámica común romana de cocción oxidante, pero en la que aún es reconocible el peso de la tradición alfarera indígena, vaccea y celtibérica. Se trata de cuatro piezas halladas en Herrera de Pisuerga (Pisoraca), lugar en el que estuvo establecida la Legión IIII Macedónica en tiempos de Augusto, que muy posiblemente estén en relación con el consumo de vino. Al menos una de ellas, la nº inv. 699, procede de una de las estancias militares del Ala Parthorum, y está fechada a finales de la época Julio-Claudia (Nerón) o, más probablemente, dentro ya de la flaviaIn this paper we are going to analyze a peculiar Roman wheel-turned cup that have been made in red clay, with painted decoration, in which the bowl is supported by an empty elevated stem over a bell foot. Is very probably that were used for the consumption of wine, like we see in the vaccaean and celtiberian traditions. In fact, the morphology of this cup type is near of many others made by those peoples. Four are the cups that in this pa-per are studied, all from the important Roman military camp situated at Herrera de Pisuerga (Pisoraca), home of the Legio IIII Macedonica in the end of 1st century BC and early 1st century AD. One of this cups, no. 699, have been found in a building of the military camp occupied by Ala Parthorum in the end of Julio-Claudian period or, more probably, in the Flavian perio

Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury

Chronic cholestatic damage is associated to both accumulation of cytotoxic levels of bile acids and expansion of adult hepatic progenitor cells (HPC) as part of the ductular reaction contributing to the regenerative response. Here, we report a bile acid-specific cytotoxic response in mouse HPC, which is partially impaired by EGF signaling. Additionally, we show that EGF synergizes with bile acids to trigger inflammatory signaling and NLRP3 inflammasome activation in HPC. Aiming at understanding the impact of this HPC specific response on the liver microenvironment we run a proteomic analysis of HPC secretome. Data show an enrichment in immune and TGF-beta regulators, ECM components and remodeling proteins in HPC secretome. Consistently, HPC-derived conditioned medium promotes hepatic stellate cell (HSC) activation and macrophage M1-like polarization. Strikingly, EGF and bile acids co-treatment leads to profound changes in the secretome composition, illustrated by an abolishment of HSC activating effect and by promoting macrophage M2-like polarization. Collectively, we provide new specific mechanisms behind HPC regulatory action during cholestatic liver injury, with an active role in cellular interactome and inflammatory response regulation. Moreover, findings prove a key contribution for EGFR signaling jointly with bile acids in HPC-mediated actions

Analytical pyrolysis evidences the presence of granaticins in the violet stains of a Roman tomb

6 páginas.-- 5 figuras.-- 14 referenciasThe walls of the Circular Mausoleum tomb (Roman Necropolis of Carmona, Spain) exhibit an important number of violet stains of unknown origin. Analytical pyrolysis detected in the tomb walls granaticin A, a violet pigment with an isobenzochromanequinone structure, as well as in the extracts of two bacterial strains isolated from the walls. The bacterium was tentatively identified as Streptomyces sp. High performance liquid chromatography confirmed that this Streptomyces synthesized as major pigments dihydrogranaticin A, granaticin A and granaticin B.This research was funded by projects GCL2010-17183 and 201230E125. M.D.H. and A.Z.M. were supported by a JAE Research Fellowship from CSIC, and a Marie Curie Intra-European Fellow-ship of the European Commission’s 7th Framework Programme(PIEF-GA-2012-328689), respectivelyPeer reviewe

Analytical pyrolysis evidences the presence of granaticins in the violet stains of a Roman tomb

The walls of the Circular Mausoleum tomb (Roman Necropolis of Carmona, Spain) exhibit an important number of violet stains of unknown origin. Analytical pyrolysis detected in the tomb walls granaticin A, a violet pigment with an isobenzochromanequinone structure, as well as in the extracts of two bacterial strains isolated from the walls. The bacterium was tentatively identified as Streptomyces sp. High performance liquid chromatography confirmed that this Streptomyces synthesized as major pigments dihydrogranaticin A, granaticin A and granaticin B.JAE Research Fellowship from CSIC GCL2010-17183 and 201230E125. M.D.H. and A.Z.M.Marie Curie Intra-European Fellowship of the European Commission’s 7th Framework Programme PIEF-GA-2012-32868

Lack of EGFR catalytic activity in hepatocytes improves liver regeneration following DDC-induced cholestatic injury by promoting a pro-restorative inflammatory response

Despite the well-known hepatoprotective role of the epidermal growth factor receptor (EGFR) pathway upon acute damage, its specific actions during chronic liver disease, particularly cholestatic injury, remain ambiguous and unresolved. Here, we analyzed the consequences of inactivating EGFR signaling in the liver on the regenerative response following cholestatic injury. For that, transgenic mice overexpressing a dominant negative mutant human EGFR lacking tyrosine kinase activity (ΔEGFR) in albumin-positive cells were submitted to liver damage induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), an experimental model resembling human primary sclerosing cholangitis. Our results show an early activation of EGFR after 1–2 days of a DDC-supplemented diet, followed by a signaling switch-off. Furthermore, ΔEGFR mice showed less liver damage and a more efficient regeneration following DDC injury. Analysis of the mechanisms driving this effect revealed an enhanced activation of mitogenic/survival signals, AKT and ERK1/2-MAPKs, and changes in cell turnover consistent with a quicker resolution of damage in response to DDC. These changes were concomitant with profound differences in the profile of intrahepatic immune cells, consisting of a shift in the M1/M2 balance towards M2 polarity, and the Cd4/Cd8 ratio in favor of Cd4 lymphocytes, overall supporting an immune cell switch into a pro-restorative phenotype. Interestingly, ΔEGFR livers also displayed an amplified ductular reaction, with increased expression of EPCAM and an increased number of CK19-positive ductular structures in portal areas, demonstrating an overexpansion of ductular progenitor cells. In summary, our work supports the notion that hepatocyte-specific EGFR activity acts as a key player in the crosstalk between parenchymal and non-parenchymal hepatic cells, promoting the pro-inflammatory response activated during cholestatic injury and therefore contributing to the pathogenesis of cholestatic liver disease. © 2022 The Pathological Society of Great Britain and Ireland.This work was supported by the Ministry of Science,Innovation and Universities (MICIU) and AgenciaEstatal de Investigacion (AEI), Spain (co-funded byFEDER funds/Development Fund–a Way to BuildEurope): RTI2018-099098-B-100 to AS/BH andRTI2018-094052-B-100 to AMV; and the RamonAreces Foundation: 20th National Competition forScientific and Technical Research in Life and MatterScience (2020) to IF. NL and JGS were recipients ofresearch assistant contracts linked to grant SAF2015-69145-R and RTI2018-099098-B-100, respectively. CMR was the recipient of a researchcontract (PEJD-2019-POST/BMD-16090) from the Education, Universities, Research and Spokesperson Counseling of the Community of Madrid

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

Study objective: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >= 4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. Results: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. Conclusion: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain