A simplified implementation of the stationary liquid mass balance method for on-line OUR monitoring in animal cell cultures

This is the peer reviewed version of the following article: [Fontova, A. , Lecina, M. , López‐Repullo, J. , Martínez‐Monge, I. , Comas, P. , Bragós, R. and Cairó, J. J. (2018), A simplified implementation of the stationary liquid mass balance method for on‐line OUR monitoring in animal cell cultures. J. Chem. Technol. Biotechnol. doi:10.1002/jctb.5551], which has been published in final form at [doi:10.1002/jctb.5551]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.BACKGROUND: Compared with other methods, the stationary liquid mass balance method for oxygen uptake rate (OUR) determination offers advantages in terms of estimation accuracy and reduction of stress. However, the need for sophisticated instrumentation, like mass flow controllers and gas analysers, has historically limited wider implementation of such a method. In this paper, a new simplified method based on inexpensive valves for the continuous estimation of OUR in animal cell cultures is evaluated. The determination of OUR values is based on accurate operation of the dissolved oxygen (DO) control loop and monitoring of its internal variables. RESULTS: The method developed was tested empirically in 2¿L bioreactor HEK293 batch cultures. OUR profiles obtained by a dynamic method, global mass balance method and the developed simplified method were monitored and compared. The results show how OUR profile obtained with the proposed method better follows the off-line cell density determination. The OUR estimation frequency was also increased, improving the method capabilities and applications. The theoretical rationale of the method was extended to the sensitivity analysis which was analytically and numerically approached. CONCLUSIONS: The results showed the proposed method to be not only cheap, but also a reliable alternative to monitor the metabolic activity in bioreactors in many biotechnological processes, being a useful tool for high cell density culture strategies implementation based on OUR monitoring.Peer ReviewedPostprint (published version

C12orf5 (chromosome 12 open reading frame 5)

Review on C12orf5, with data on DNA/RNA, on the protein encoded and where the gene is implicated

PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2)

Review on PFKFB2, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Dual Costimulatory and Coinhibitory Targeting with a Hybrid Fusion Protein as an Immunomodulatory Therapy in Lupus Nephritis Mice Models

Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains: CTLA4, blocking the CD28-CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1-PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy

Anàlisi del descens de la natalitat durant la pandèmia de la COVID-19 a l’Alt Empordà

Natalitat; COVID-19; Hospital comarcalNatalidad; COVID-19; Hospital comarcalNatality; COVID-19; Country hospitalS'entén per natalitat el nombre de nascuts vius que es produeix en un territori. Aquesta dada unida a l'estadística de defuncions permet estimar el creixement de la població. A la comarca de l'Alt Empordà hi ha hagut un increment significatiu de la població immigrada en els últims anys, fins a situar-se actualment a prop del 25%. Aquest fet ha impactat tant en el creixement de la població com també en la natalitat en els darrers anys, una situació que s’ha alterat amb la COVID-19. L’objectiu d’aquest estudi va ser comparar el nombre de parts a la Fundació Salut Empordà (FSE) el 2022 respecte al període 2020-2021 i analitzar l’evolució de la taxa de naixements a la comarca de l’Alt Empordà durant el període 1998-2022

Key Figures on Alt Empordà 2022

Demografia; Salut; Economia; TerritoriDemografía; Salud; Economía; TerritorioDemographics; Health; Economy; TerritoryIndicadors Clau de l’Alt Empordà 2022 presenta una selecció de dades estadístiques sobre l’Alt Empordà i la demarcació de Girona. Aquestes dades s’emmarquen en l’àmbit municipal en tots aquells casos en què ha estat possible i, en altres en què no s’ha pogut obtenir informació prou detallada, es presenten en àmbit comarcal o provincial. En aquest document es vol aportar una visió general que faciliti conèixer l’estat del territori amb dades de l’any 2021 o les més recents editades, i veure quines són les tendències actuals. El recull inclou dades sociodemogràfiques, de salut, d’economia, de medi ambient i d’altres recursos del territori. En l’edició de 2022, com ja passava l’any anterior, s’objectiva la influència de l'epidèmia de COVID-19 en diversos indicadors i tendències.Indicadores Clave del Alt Empordà 2022 presenta una selección de datos estadísticos sobre el Alt Empordà y la demarcación de Girona. Estos datos se enmarcan en el ámbito municipal en todos aquellos casos en los que ha sido posible y, en los que no se ha podido obtener información lo suficientemente detallada, se presentan en ámbito comarcal o provincial. En este documento se quiere aportar una visión general que facilite conocer el estado del territorio con datos del año 2021 o más recientes editados, y ver cuáles son las tendencias actuales. La recopilación incluye datos sociodemográficos, de salud, de economía, de medio ambiente y otros recursos del territorio. En la edición de 2022, como ya pasaba el año anterior, se objetiva la influencia de la epidemia de COVID-19 en varios indicadores y tendencias.Key Figures on Alt Empordà 2022 presents a selection of statistics on Alt Empordà and the province of Girona. Whenever possible, this data is defined within the municipal scope, but in many cases, it has not been possible to obtain sufficiently detailed information, so the figures are for the whole area or provincial. This document aims to provide a general view to help us find out about the state of the area using 2021 data or the most recent data available and identifying current trends. This document includes data on demographics, socio-demographics, health, economy, the territory and its resources. As was the case last year, in the 2022 edition, the influence of the COVID-19 epidemic has been objectified in various indicators and trends

Cytotoxicity of osmium(ii) and cycloosmated half-sandwich complexes from 1-pyrenyl-containing phosphane ligands

Five metal-arene complexes of formula [MX2(η6-p-cymene)(diR(1-pyrenyl)phosphane)] (M = Os or Ru, X = Cl or I, R = isopropyl or phenyl) and symbolized as MRX2 were synthesized and fully characterized, namely OsiPrCl2, OsiPrI2, OsPhCl2, OsPhI2 and RuPhI2. Furthermore, nine cyclometalated half-sandwich complexes of formula [MX-(η6-p-cymene)(k2C-diR(1-pyrenyl)phosphane)] (M = Os or Ru, X = Cl or I, R = isopropyl or phenyl) or [M(η6-p-cymene)(kS-dmso)(k2C-diR(1-pyrenyl)phosphane)]PF6 (M = Os or Ru, R = isopropyl or phenyl) and symbolized as c-MRX were prepared; hence, c-OsiPrCl, c-OsiPrI, c-OsiPrdmso, c-OsPhCl, c-OsPhI, c-OsPhdmso, c-RuPhCl, c-RuPhI and c-RuPhdmso were obtained and fully characterized. The crystal structures of ten out of the fourteen complexes were solved. All complexes exhibit notable cytotoxic properties against A549 (Lung Adenocarcinoma) human cells, with IC50 values ranging from 48 to 1.42 μM. In addition, complex c-OsiPrdmso shows remarkable toxic behaviours agains other cell lines, namely MCF7 (breast carcinoma), MCF10A (non-tumorigenic epithelial breast) and MDA-MB-435 (melanoma) human cells, as illustrated by IC50 values of 4.36, 4.71 and 2.32 μM, respectively. Finally, it has been found that OsiPrI2 affects the cell cycle of A549 cells, impeding their replication (i.e., the cell cycle is blocked), whereas OsPhI2 (namely with phenyl groups instead of isopropyl ones) does not induce this effect

Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)2}2+ moiety and a third sterically non-hindering bidentate ligand, namely 2,2'-dipyridylamine (dpa) and N-benzyl-2,2'-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)2(dpa)](PF6)2 (1) and [Ru(phen)2(Bndpa)](PF6)2 (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic 'parent' compound [Ru(phen)3](PF6)2, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050-430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions

Small molecule anion carriers facilitate lactate transport in model liposomes and cells

An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we present a family of anionophores based on the structure of click-tambjamines that have proved to be extremely active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. Moreover, an additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism

Evolució de la mortalitat durant la pandèmia de COVID-19 a un hospital comarcal (2020-2022)

Mortalitat; COVID-19; Hospital comarcalMortalidad; COVID-19; Hospital comarcalMortality; COVID-19; County hospitalL’objectiu de l’estudi va ser conèixer les causes de mortalitat i la seva evolució en el període d’aparició de la COVID-19 en un hospital comarcal