Development of robotic technology platform for intellectual repair of road load

The work is devoted to the creation of a robotic complex capable of automated repair of the roadway, in particular pits. The robot should be autonomous, but you need to take into account the possibility of instant interception of control

Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells

Liposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers.This work has received funding from the European Union's Seventh Framework Program (FP7/2007-2013; grant agreement NMP4-LA-2009-228827 NANOFOL) and Horizon 2020 Research and Innovation Program (grant agreement No 683356 - FOLSMART), further from the Portuguese Foundation for Science and Technology under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020.info:eu-repo/semantics/publishedVersio

TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms

[EN] Objective Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor signalling, protecting the liver from various hepatotoxic injuries, yet its role in liver cancer is poorly defined. Here, we investigated the impact of TREM-2 on liver regeneration and hepatocarcinogenesis. Design TREM-2 expression was analysed in liver tissues of two independent cohorts of patients with HCC and compared with control liver samples. Experimental HCC and liver regeneration models in wild type and Trem-2-/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids were conducted. Results TREM-2 expression was upregulated in human HCC tissue, in mouse models of liver regeneration and HCC. Trem-2-/- mice developed more liver tumours irrespective of size after diethylnitrosamine (DEN) administration, displayed exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. Administering an antioxidant diet blocked DEN-induced hepatocarcinogenesis in both genotypes. Similarly, Trem-2-/- animals developed more and larger tumours in fibrosis-associated HCC models. Trem-2-/- livers showed increased hepatocyte proliferation and inflammation after partial hepatectomy. Conditioned media from human HSCs overexpressing TREM-2 inhibited human HCC spheroid growth in vitro through attenuated Wnt ligand secretion. Conclusion TREM-2 plays a protective role in hepatocarcinogenesis via different pleiotropic effects, suggesting that TREM-2 agonism should be investigated as it might beneficially impact HCC pathogenesis in a multifactorial manner.Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud Carlos III’ grants (MJP (PI14/00399, PI17/00022 and Ramon y Cajal Programme RYC-2015–17755); JMB (PI12/00380, PI15/01132, PI18/01075, Miguel Servet Programme CON14/00129 and CPII19/00008) cofinanced by ’Fondo Europeo de Desarrollo Regional’ (FEDER); CIBERehd: MJP, JMB and LB), Spain; IKERBASQUE, Basque foundation for Science (MJP and JMB), Spain; ’Diputación Foral de Gipuzkoa’ (MJP: DFG18/114, DFG19/081; JMB: DFG15/010, DFG16/004); BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/ BD to JMB); Department of Health of the Basque Country (MJP: 2015111100 and 2019111024; JMB: 2017111010), Euskadi RIS3 (JMB: 2016222001, 2017222014, 2018222029, 2019222054, 2020333010) Department of Industry of the Basque Country (JMB: Elkartek: KK-2020/00008) and AECC Scientific Foundation (JMB). AE-B was funded by the University of the Basque Country (UPV/EHU) (PIF2014/11) and by the short-term training fellowship Andrew K Burroughs (European Association for the Study of the Liver, EASL). IL and AA-L were funded by the Department of Education, Language Policy and Culture of the Basque Government (PRE_2016_1_0152 and PRE_2018_1_0184). OS and SK were funded by the Austrian Science Fund (FWF25801-B22, FWF-P35168 to OS and L-Mac: F 6104-B21 to SK). FO and DAM were funded by a UK Medical Research Council programme Grant MR/R023026/1. DAM was also funded by the CRUK programme grant C18342/A23390, CRUK/AECC/AIRC Accelerator Award A26813 and the MRC MICA programme grant MR/R023026/1. JBA is supported by the Danish Medical Research Council, Danish Cancer Society, Nordisk Foundation, and APM Foundation. CJO’R and PM-G are supported by Marie Sklodowska-Curie Programme and EASL Sheila Sherlock postdoctoral fellowships

Polymicrobial sepsis models: CLP versus CASP

Sepsis is a disease syndrome covering many different aspects of the host immune system. Our understanding of sepsis is still incomplete. Several animal models of sepsis have been developed and much of our current knowledge on the molecular basis of the disease has originated from these models. Two of the most reliable and clinically relevant rodent models to mimic human sepsis in the animal model are cecal ligation and puncture (CLP) and colon ascendens stent peritonitis (CASP)

Insulin hypersensitivity induced by hepatic PTEN gene ablation protects from murine endotoxemia.

Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPARγ and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes