Abstract
The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different ...isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology. The transcriptomic study was performed by RT-PCR using samples of amygdala, anterior hippocampus, posterior hippocampus, claustrum, calcarine fissure, globus pallidus and cerebellum from patients with mild, moderate, or severe AD, as well as healthy individuals. Certain heparan sulfate epitopes were also detected by immunohistochemistry. Several genes, across all stages of heparan sulfate synthesis, showed altered transcription in different brain regions of AD patients. The numbers of alterations were greater in in moderate versus mild AD patients. In severe patients, there were fewer alterations in genes related to early stages of biosynthesis, and overexpression of genes involved in late stages. The alterations correlated with progressive brain atrophy, although alterations were more common in the cerebellum. Detection of some heparan sulfate epitopes by immunohistochemistry was consistent with previous studies. In conclusion, transcriptional alterations in the biosynthetic genes of heparan sulfate depend on the brain region and the degree of AD pathology.
Glioblastoma stands as the most frequent primary brain tumor. Despite the multimodal therapy for glioblastoma patients, the survival rate is very low, highlighting the need for novel therapies that ...improve patient outcomes. Immune checkpoint blockade strategies are achieving promising results in a myriad of tumors and several studies have reported its efficacy in glioblastoma at a preclinical level. ILT2 is a novel immune checkpoint that exerts an inhibitory effect via the interaction with classical and non‐classical HLA class‐I molecules. Herein, we report that ILT2 blockade promotes antitumor responses against glioblastoma. In silico and immunohistochemical analyses revealed that the expression of ILT2 and its ligands HLA‐A, ‐B, ‐C, and ‐E are highly expressed in patients with glioblastoma. Disruption of ILT2 with blocking monoclonal antibodies increased natural killer cell‐mediated IFN‐γ production and cytotoxicity against glioblastoma, partially reverting the immunosuppression linked to this malignancy. In addition, co‐treatment with temozolomide strengthened the antitumor capacity of anti‐ILT2‐treated immune cells. Collectively, our results establish the basis for future studies regarding the clinical potential of ILT2 blockade alone or in combination regimens in glioblastoma.
The inhibitory immune checkpoint ILT2 is highly expressed in glioblastoma. Its blockade partially restores antitumor responses in this tumor and combination with temozolomide enhances this anti‐glioblastoma effect.
Los reactores de investigación juegan un papel fundamental en el desarrollo de las aplicaciones pacíficas de la energía nuclear. Este aporte incluye su participación en la medicina, industria, ...ciencia, investigación y educación. Por ello, y con la finalidad de aprovechar al máximo su utilización, se requiere de una planificación estratégica. Para tal fin, se empleó la herramienta FODA como base del análisis estratégico y del planeamiento requerido en la gestión de la utilización de los reactores de investigación, cuyo resultado permite identificar las necesidades de todas las partes interesadas y gestionar el impacto de estas para una oportuna toma de decisiones. El objetivo es garantizar la continuidad del funcionamiento seguro y sostenible del reactor de investigación existente en el marco de potenciales inversiones por modificaciones y ampliaciones en sus instalaciones.
The study aimed to identify predictors of overall 30-day mortality in cancer patients with pulmonary embolism including suspected pulmonary embolism (SPE) and unsuspected pulmonary embolism (UPE) ...events. Secondary outcomes included 30- and 90-day major bleeding and venous thromboembolism (VTE) recurrence.The study cohort included 1033 consecutive patients with pulmonary embolism from the multicentre observational ambispective EPIPHANY study (March 2006-October 2014). A subgroup of 497 patients prospectively assessed for the study were subclassified into three work-up scenarios (SPE, truly asymptomatic UPE and UPE with symptoms) to assess outcomes.The overall 30-day mortality rate was 14%. The following variables were associated with the overall 30-day mortality on multivariate analysis: VTE history, upper gastrointestinal cancers, metastatic disease, cancer progression, performance status, arterial hypotension <100 mmHg, heart rate >110 beats·min
, basal oxygen saturation <90% and SPE (versus overall UPE).The overall 30-day mortality was significantly lower in patients with truly asymptomatic UPE events (3%) compared with those with UPE-S (20%) and SPE (21%) (p<0.0001). Thirty- and 90-day VTE recurrence and major bleeding rates were similar in all the groups.In conclusion, variables associated with the severity of cancer and pulmonary embolism were associated with short-term mortality. Our findings may help to develop pulmonary embolism risk-assessment models in this setting.
Heparan sulfate proteoglycans (HSPGs) are complex molecules which play a role in the invasion and growth and metastatic properties of cancerous cells. In this work we analyze changes in the patterns ...of expression of HSPGs in left sided colorectal cancer (LSCRC), both metastatic and non-metastatic, and the results are also compared with those previously obtained for right sided tumors (RSCRCs).
Eighteen LSCRCs were studied using qPCR to analyze the expression of both the proteoglycan core proteins and the enzymes involved in heparan sulfate chain biosynthesis. Certain HSPGs also carry chondroitin sulfate chains and so we also studied the genes involved in its biosynthesis. The expression of certain genes that showed significant expression differences were also analysed using immunohistochemical techniques.
Changes in proteoglycan core proteins were dependent on their location, and the main differences between metastatic and non-metastatic tumors affected cell-surface glypicans, while other molecules were quite similar. Glypicans were also responsible for the main differences between RS- and LS- malignances. Regarding the biosynthesis of heparan sulfate chains, differential alterations in transcription depending on the presence or not of metastasis affected genes involved in the modification of uronic acid (epimerization and 2-O sulfation), and some isoforms responsible for sulfation of glucosamine (NDST1, HS6ST1). Moreover, in RSCRCs differences were preferentially found in the expression of genes involved in C6 and C3 sulfation of glucosamine, but not in NDSTs or SULFs. Finally, synthesis of chondroitin sulfate showed some alterations, which affected various steps, including polimerization and the modification of chains, but the main variations dependent on the presence of metastases were epimerization and 6C sulfation; however, when compared with RSCRCs, the essential divergences affected polymerization of the chains and the 6C sulfation of the galactosamine residue.
We evidenced alterations in the expression of HSPGs, including the expression of cell surface core proteins, many glycosiltransferases and some enzymes that modify the GAG chains in LSCRCs, but this was dependent on the metastatic nature of the tumor. Some of these alterations are shared with RSCRCs, while others, focused on specific gene groups, are dependent on tumor localization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
El estudio en cuestión aborda la repercusión económica de la pandemia de COVID-19 en el ámbito turístico ecuatoriano entre 2020 y 2022, enfocándose en las perturbaciones que enfrentó esta esfera ...tanto antes como después del brote. A fin de trazar la trayectoria de los ingresos turísticos en relación con el PIB del sector, se escrutaron datos de informes trimestrales procedentes del Ministerio de Turismo del Ecuador, el Banco Central y la CEPAL. La investigación reveló una merma notable en dichos ingresos, consecuencia directa de las medidas de restricción de movilidad instauradas por el Gobierno con el propósito primordial de proteger la salud pública. Al desglosar los factores, emergió que aspectos como los ingresos generados por la venta de alimentos, el alojamiento hotelero y las intermediaciones de agencias de viajes influenciaron, tanto positiva como negativamente, el crecimiento del PIB turístico. Es crucial subrayar que, en el contexto pandémico, estas dinámicas contravinieron las expectativas convencionales. La conclusión esclarece que, si bien el 2020 representó un obstáculo sustancial para la reactivación turística, a raíz de las medidas de contención y seguridad, en los subsiguientes años, 2021 y 2022, el sector evidenció signos palpables de recuperación.
Palabras clave: Turismo; Restricciones; Contraste; Impacto; Informes.
The purpose of this research is to identify the plant trap that promote of arbuscular mycorrhizae development, to select an efficient substrate for AM propagation and for the determination of the ...most efficient interaction study factors to propagate arbuscular mycorrhizae. This study was based on macro analysis methodologies and microscopic plant tissue and MA isolation protocol taking into account inoculum production studios. As a result, it was established: For the plant height variable a difference is made highly significant for factor trap plant factor, highly significant differences for substrate factor and highly significant difference for the interaction of trap plants substrates, which by the Tukey test at 5% stands out as better treatment t5 which corresponds to the ryegrass cultivation in clay and rice husk, which was identified more plant growth at 30, 60 and 90 days, with an average of 37.8 cm plant height. For the variable fresh and dry weight of foliage as well as the fresh weight of root mass provides highly significant differences for trap plants factor, significant difference for substrate factor and highly significant difference for the interaction of the factors trap plants substrates, with DMS test it states that the best trap plant was (Raygrás).
Small leucine-rich proteoglycans (SLRPs) regulate different processes and undergo significant alterations in various diseases. Colon carcinomas (CCs) are heterogeneous pathologies with important ...clinical and molecular differences depending on their location, which makes it interesting to analyze the alterations in SLRPs in right- and left-sided tumors (RS- and LSCCs). SLRP transcription levels were studied in 32 CCs using qPCR compared to healthy colon mucosae samples from the same patients, 20 of them from LSCCs and the remaining 12 from RSCCs. Protein expression of genes with significant differences in their transcriptions was analyzed by immunohistochemistry. The alterations observed were related to survival data. The arrangement of transcription of SLRPs was quite similar in ascending and descending colon, but RS- and LSCCs displayed different patterns of alteration, with a greater number of deregulations occurring in the latter. The analysis of protein expression also indicated changes in the location of these molecules, largely moving to the cell interior. While podocan underexpression showed a trend toward better outcomes, no differences were observed in terms of overall survival. In vitro studies using the HT29 tumor cell line suggest that deregulation of SLRPs could affect cell proliferation. SLRPs constitute new differential markers of RS- and LSCCs, showing differences dependent on the anatomical location of the tumor.
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