Monocyte-endothelial cell interactions in the regulation of vascular sprouting and liver regeneration in mouse

Background & Aims Regeneration of the hepatic mass is crucial to liver repair. Proliferation of hepatic parenchyma is intimately dependent on angiogenesis and resident macrophage-derived cytokines. However the role of circulating monocyte interactions in vascular and hepatic regeneration is not well-defined. We investigated the role of these interactions in regeneration in the presence and absence of intact monocyte adhesion. Methods Partial hepatectomy was performed in wild-type mice and those lacking the monocyte adhesion molecule CD11b. Vascular architecture, angiogenesis and macrophage location were analyzed in the whole livers using simultaneous angiography and macrophage staining with fluorescent multiphoton microscopy. Monocyte adhesion molecule expression and sprouting-related pathways were evaluated. Results Resident macrophages (Kupffer cells) did not migrate to interact with vessels whereas infiltrating monocytes were found adjacent to sprouting points. Infiltrated monocytes colocalized with Wnt5a, angiopoietin 1 and Notch-1 in contact points and commensurate with phosphorylation and disruption of VE-cadherin. Mice deficient in CD11b showed a severe reduction in angiogenesis, liver mass regeneration and survival following partial hepatectomy, and developed unstable and leaky vessels that eventually produced an aberrant hepatic vascular network and Kupffer cell distribution. Conclusions Direct vascular interactions of infiltrating monocytes are required for an ordered vascular growth and liver regeneration. These outcomes provide insight into hepatic repair and new strategies for hepatic regeneration.National Institutes of Health (U.S.) (Grant R01 GM 49039

Función de la vía de señalización Notch en el desarrollo del sistema hematopoyético

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21-07-0

Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment

Objective: Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment. Design: Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op. Results: Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment. Conclusions: Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation

Single-Walled Carbon Nanohorns as Promising Nanotube-Derived Delivery Systems to Treat Cancer

Cancer has become one of the most prevalent diseases worldwide, with increasing incidence in recent years. Current pharmacological strategies are not tissue-specific therapies, which hampers their efficacy and results in toxicity in healthy organs. Carbon-based nanomaterials have emerged as promising nanoplatforms for the development of targeted delivery systems to treat diseased cells. Single-walled carbon nanohorns (SWCNH) are graphene-based horn-shaped nanostructure aggregates with a multitude of versatile features to be considered as suitable nanosystems for targeted drug delivery. They can be easily synthetized and functionalized to acquire the desired physicochemical characteristics, and no toxicological effects have been reported in vivo followed by their administration. This review focuses on the use of SWCNH as drug delivery systems for cancer therapy. Their main applications include their capacity to act as anticancer agents, their use as drug delivery systems for chemotherapeutics, photothermal and photodynamic therapy, gene therapy, and immunosensing. The structure, synthesis, and covalent and non-covalent functionalization of these nanoparticles is also discussed. Although SWCNH are in early preclinical research yet, these nanotube-derived nanostructures demonstrate an interesting versatility pointing them out as promising forthcoming drug delivery systems to target and treat cancer cells

Nanoparticles to Target and Treat Macrophages:The Ockham's Concept?

Nanoparticles are nanomaterials with three external nanoscale dimensions and an average size ranging from 1 to 1000 nm. Nanoparticles have gained notoriety in technological advances due to their tunable physical, chemical, and biological characteristics. However, the administration of functionalized nanoparticles to living beings is still challenging due to the rapid detection and blood and tissue clearance by the mononuclear phagocytic system. The major exponent of this system is the macrophage. Regardless the nanomaterial composition, macrophages can detect and incorporate foreign bodies by phagocytosis. Therefore, the simplest explanation is that any injected nanoparticle will be probably taken up by macrophages. This explains, in part, the natural accumulation of most nanoparticles in the spleen, lymph nodes, and liver (the main organs of the mononuclear phagocytic system). For this reason, recent investigations are devoted to design nanoparticles for specific macrophage targeting in diseased tissues. The aim of this review is to describe current strategies for the design of nanoparticles to target macrophages and to modulate their immunological function involved in different diseases with special emphasis on chronic inflammation, tissue regeneration, and cancer

Türkiye: macro-financial situation

Rationale Türkiye is identified annually as a material country for the Spanish and euro area banking systems. Moreover, both are linked to Türkiye by major trade and financial flows. It is therefore important to monitor the country’s macro-financial situation and main weaknesses. Takeaways •The Turkish economy has continued to post very high, albeit slowing, inflation rates since late 2022, and economic activity has slowed, against a background of sizeable external financing needs, foreign currency debt and low international reserves. •Fiscal policy kept the country’s accounts healthy in 2022, although a significant downturn is expected in 2023. In terms of monetary policy, the Central Bank of the Republic of Türkiye cut the policy interest rate again in February, with the real interest rate standing at -35.2% in April. •The banking system remains healthy, although some indicators have worsened. Furthermore, to keep credit growth in check and encourage more widespread use of the lira in the financial system, the macroprudential and regulatory measures introduced in 2021 and 2022 remained in place and were strengthened

Guía para realizar pruebas de laboratorio en materiales para terracerias y pavimentos

1 archivo PDF (69 páginas)"Se describen las pruebas que pueden considerarse indispensables realizar a los materiales susceptibles de utilizarse en la tecnología de las vías terrestres, pruebas que proporcionan los datos necesarios para conocer la calidad de los suelos, la humedad óptima, y poder calcular el grado de compactación, así como el comportamiento al ejercer sobre él cargas dinámicas, parámetros que nos ayudan en el diseño de los espesores de la diversas capas en que quedará estructurada una obra vial, tales como el cuerpo del terraplén, sub-rasante, sub-base, base y carpeta, tratándose de carreteras y aeropuertos, o el sub-balasto y balasto en ferrocarriles.

Prediction of the flame kernel growth rate in spark ignition engine fueled with natural gas, hydrogen and mixtures

Producción CientíficaThe knowledge of combustion duration is a key tool in the development of engines, specially nowadays for engines adapted to new fuels with low C/H ratio such as natural gas and hydrogen. This work is aimed to develop a correlation that predicts the duration of the first phase of combustion until the process becomes turbulent in a SI engine. The flame kernel radius when this transition occurs, , is the study variable. To determine this variable from the experimental pressure records, a flame kernel growth predictive model is used. The predictive model is adjusted to the experimental data, determining the most appropriate value. The pressure records of 500 consecutive cycles of 48 test points have been processed. The averaged values of of each test point have been correlated with the characteristic parameters of the process: turbulence and properties of the fuel–air mixtures. Finally, and integral length scale ratio is correlated with Damköhler number. A wide range of operating conditions have been studied, reaching the novel conclusion that it is possible to analyze the kernel growth phenomenon from a spatial point of view rather than from a temporal point of view, as had been studied in many previous works. The developed correlation can be used in combustion predictive modeling to support SI engine design. Other practical conclusion from the work, that can be used in SI engine development, is that decreasing the integral length scale reduces the time of the first phase of combustion.Ministerio de Ciencia e Innovación (PID2019-106957RB-C22). “Analysis and characterization of dual fuel combustion for the reduction of CO2 emissions in the transport sector

Biotinylated polyurethane-urea nanoparticles for targeted theranostics in human hepatocellular carcinoma

Over the past years, significant efforts have been devoted to explore novel drug delivery and detection strategies for simultaneous therapy and diagnostics. The development of biotinylated polyurethane-urea nanoparticles as theranostic nanocarriers for targeted drug and plasmid delivery, for fluorescence detection of human hepatocellular carcinoma cells, is described herein. These targeted nanoparticles are specifically designed to incorporate biotin into the polymeric matrix, since many tumor types overexpress receptors for biotin as a mechanism to boost uncontrolled cell growth. The obtained nanoparticles were spherical, exhibited an average diameter ranging 110–145 nm, and showed no cytotoxicity in healthy endothelial cells. Biotinylated nanoparticles are selectively incorporated into the perinuclear and nuclear area of the human hepatocellular carcinoma cell line, HepG2, in division, but not into growing, healthy, human endothelial cells. Indeed, the simultaneous incorporation of the anticancer drugs, phenoxodiol or sunitinib, together with plasmid DNA encoding green fluorescent protein, into these nanoparticles allows a targeted pharmacological antitumor effect and furthermore, selective transfection of a reporter gene, to detect these cancer cells. The combined targeted therapy and detection strategy described here could be exploited for liver cancer therapy and diagnostics, with a moderate safety profile, and may also be a potential tool for other types of cancer.Spain. Ministerio de Educación y CienciaDGI (Spain) (CTQ 2011-29336-C03/PPQ)Catalonia (Spain). Departament d'Universitats, Recerca i Societat de la Informació (DURSI) (Grant 2009 SGR-961)CIBER-BB