Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB

<p>Abstract</p> <p>Background</p> <p>Captopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the treatment of arterial hypertension and cardiovascular diseases. Our objective was to study whether captopril is able to attenuate the cardiac inflammatory process associated with arterial hypertension.</p> <p>Methods</p> <p>Left ventricle mRNA expression and plasma levels of pro-inflammatory (interleukin-1β (IL-1β) and IL-6) and anti-inflammatory (IL-10) cytokines, were measured in spontaneously hypertensive rats (SHR) and their control normotensive, Wistar-Kyoto (WKY) rats, with or without a 12-week treatment with captopril (80 mg/Kg/day; n = six animals per group). To understand the mechanisms involved in the effect of captopril, mRNA expression of ACE, angiotensin II type I receptor (AT1R) and p22phox (a subunit of NADPH oxidase), as well as NF-κB activation and expression, were measured in the left ventricle of these animals.</p> <p>Results</p> <p>In SHR, the observed increases in blood pressures, heart rate, left ventricle relative weight, plasma levels and cardiac mRNA expression of IL-1β and IL-6, as well as the reductions in the plasma levels and in the cardiac mRNA expression of IL-10, were reversed after the treatment with captopril. Moreover, the mRNA expressions of ACE, AT1R and p22phox, which were enhanced in the left ventricle of SHR, were reduced to normal values after captopril treatment. Finally, SHR presented an elevated cardiac mRNA expression and activation of the transcription nuclear factor, NF-κB, accompanied by a reduced expression of its inhibitor, IκB; captopril administration corrected the observed changes in all these parameters.</p> <p>Conclusion</p> <p>These findings show that captopril decreases the inflammation process in the left ventricle of hypertensive rats and suggest that NF-κB-driven inflammatory reactivity might be responsible for this effect through an inactivation of NF-κB-dependent pro-inflammatory factors.</p

T1 bladder carcinoma with variant histology: pathological features and clinical significance

The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder

Holistic overview of natural ventilation and mixed mode in built environment of warm climate zones and hot seasons

The climate change leads to periods of extreme events (i.e. reduction of cold seasons, heat waves, overheating, urban heat island among others) that affect the performance of residential and tertiary buildings with high occupancy (i.e. hospitals, schools, commercial centres, offices etc). However, most of low-carbon policies do not consider the ventilation as a mitigation measure. In fact, a lack of studies on natural ventilation (NV) and mixed-mode (MM) strategies was detected, especially for warm regions or areas with hot and humid climates. This paper aims to carry out a bibliometric analysis from 1928 to 2023, to observe the evolution of the topic. After identifying the main research clusters (thermal comfort, energy efficiency, indoor air quality and simulation tools) by science mapping, the most relevant publications of the last 20 years were assessed (2003–2023). The results of this study revealed that only 1.51 % of the scientific documents in 95 years corresponded to an extensive literature review, although epidemic or disease outbreaks led to peaks of production in this topic. This emphasizes the importance of observing what was done and how was implemented over the years. Regarding the clusters, some relevant aspects can be highlighted: (i) non-homogeneity of studies on NV or MM related to building type; (ii) interregional projects should be drawn up to check the effectiveness of NV and MM, especially when other architectural techniques are adopted (i.e. solar chimneys, window wall ratio –WWR-, thermally activated building structures –TABS- etc); (iii) the optimization of simulation tools should be based on the incorporation of BIM and generative design for NV and MM

High-throughput SNP genotyping in Cucurbita pepo for map construction and quantitative trait loci mapping

Background: Cucurbita pepo is amember of the Cucurbitaceae family, the second-most important horticultural family in terms of economic importance after Solanaceae. The ¿summer squash¿ types, including Zucchini and Scallop, rank among the highest-valued vegetables worldwide. There are few genomic tools available for this species. The first Cucurbita transcriptome, along with a large collection of Single Nucleotide Polymorphisms (SNP), was recently generated using massive sequencing. A set of 384 SNP was selected to generate an Illumina GoldenGate assay in order to construct the first SNP-based genetic map of Cucurbita and map quantitative trait loci (QTL). Results: We herein present the construction of the first SNP-based genetic map of Cucurbita pepo using a population derived from the cross of two varieties with contrasting phenotypes, representing the main cultivar groups of the species¿ two subspecies: Zucchini (subsp. pepo) ¿ Scallop (subsp. ovifera). The mapping population was genotyped with 384 SNP, a set of selected EST-SNP identified in silico after massive sequencing of the transcriptomes of both parents, using the Illumina GoldenGate platform. The global success rate of the assay was higher than 85%. In total, 304 SNP were mapped, along with 11 SSR from a previous map, giving a map density of 5.56 cM/marker. This map was used to infer syntenic relationships between C. pepo and cucumber and to successfully map QTL that control plant, flowering and fruit traits that are of benefit to squash breeding. The QTL effects were validated in backcross populations. Conclusion: Our results show that massive sequencing in different genotypes is an excellent tool for SNP discovery, and that the Illumina GoldenGate platform can be successfully applied to constructing genetic maps an performing QTL analysis in Cucurbita. This is the first SNP-based genetic map in the Cucurbita genus and is an invaluable new tool for biological research, especially considering that most of these markers are located in the coding regions of genes involved in different physiological processes. The platform will also be useful for future mapping and diversity studies, and will be essential in order to accelerate the process of breeding new and better adapted squash varieties.This research was funded by the INIA projects RTA2008-00035-C02-01/02 and RTA2011-00044-C02-1/2 of the Spanish Instituto Nacional de Investigacion y Tecnologia Agraria and FEDER funds (EU). The NVD grant was supported by the Programa de Formacion del Personal Tecnico e Investigador from IFAPA, co-financed with European Social Funds. The authors wish to thank P. Salas and E. Martinez Perez for their technical assistance in the fruit characterization. We are thankful for the kindly suggestions of Dr. Harry Paris for the F2 C. pepo mapping population.Esteras Gómez, C.; Gómez, P.; Monforte Gilabert, AJ.; Blanca Postigo, JM.; Vicente-Dolera, N.; Roig Montaner, MC.; Nuez Viñals, F.... (2012). High-throughput SNP genotyping in Cucurbita pepo for map construction and quantitative trait loci mapping. BMC Genomics. 13(80):1-21. https://doi.org/10.1186/1471-2164-13-80S121138

Impact of FLT3–ITD mutation status and its ratio in a cohort of 2901 patients undergoing upfront intensive chemotherapy: a PETHEMA registry study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3–ITD-mutated patients, median OS gradually decreased according to FLT3–ITD status and ratio (34.3 months FLT3–ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3–ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3–ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations

Loss of heterozygosity at 9q32-33 (DBC1 locus) in primary non-invasive papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma of the bladder and their associated normal urothelium.

Tumour recurrence has a major impact on patients with non-invasive papillary urothelial tumours of the bladder. To explore the role of DBC1 (deleted in bladder cancer 1 locus), a candidate tumour suppressor gene located at 9q32–33, as prognostic marker we have performed loss of heterozygosity (LOH) testing in 49 patients with primary papillary urothelial tumours and associated normal urothelium. Data from the 38 tumours and 11 specimens of normal urothelium that were informative in the LOH study (D9S195 marker) showed that LOH in urothelium (45.4%) but not in non-invasive tumours (60.5%) was associated with tumour recurrence (p = 0.026) but not to grade or progression. Also, tumours whose normal urothelium had LOH were larger (p = 0.020) and showed cyclin D1 over-expression (p = 0.032). Non-significant increased expression of p53, p21Waf1, apoptotic index and tumour proliferation, and decreased expression of p27Kip1 or cyclin D3 also characterized tumours whose normal urothelium had LOH. The expression of these G1 –S modulators, apoptotic index and tumour proliferation was more heterogeneous in papillary urothelial tumours, irrespective of having retained heterozygosity or LOH. Also, Bax expression decreased in papillary urothelial tumours having LOH (p = 0.0473), but Bcl-2 was unrelated to LOH status. In addition, FGFR3 protein expression decreased in LOH tumours (p = 0.036) and in those having LOH in their normal urothelium (p = 0.022). FGFR3 immunohistochemical expression was validated by western blot in selected cases. The survival analysis selected LOH in normal urothelium as a marker of disease-free survival (log-rank 5.32, p = 0.021), progression-free survival (log-rank 3.97, p = 0.046) and overall survival (log-rank 4.26, p = 0.038); LOH in tumours was significant in progression-free survival (log-rank 3.83, p = 0.042). It is concluded that LOH at the DBC1 locus in normal urothelium seems to be relevant in the prognosis of non-invasive papillary tumours of the bladder via selecting cases with increased proliferation, frequent alterations of the G1 –S phase modulators, and decreased FGFR3 protein expression

Tailoring of magnetocaloric response in nanostructured materials: Role of anisotropy

The magnetocaloric response of an ensemble of oriented uniaxial magnetic objects, perpendicularly magne- tized to their easy axes, for temperatures close to the blocking temperature is calculated with the aim of demonstrating that the control of the sample’s microstructure makes up an effective way to tailor its magne- tocaloric response. Coexisting positive and negative magnetocaloric effect (MCE) is found for a model mate- rial with a single magnetic phase transition. Both MCE regimes are controlled by the magnitude of the applied magnetic field. As a proof of concept, experimental results for arrays of self-assembled ferromagnetic nano- wires embedded into highly ordered nanoporous anodic alumina templates are shown, suggesting the validity of the numerical calculations

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-Aim of study: Soil degradation in agricultural areas is a widespread problem. In this framework, a data validation methodology is pre-sented, including a study of the spatial resolution of Global Navigation Satellite System (GNSS) measurements, the calculation of erosion/deposition models, and the contribution of dual frequency and low-cost single frequency GNSS receivers. Area of study: A test olive grove in SE Spain.Material and methods: The study is based on three observation campaigns, between 2016 and 2018, using different GNSS receivers and working modes. The comparison between different surveys provide the volumetric variation over the analyzed period. Main results: Considering the dual-frequency receiver, there was no statistically significant difference between the means and the va-riances from 1.5 m and from 4.5 m data resolution at the 0.05 significance level. In order to estimate vertical differences from successive GNSS campaigns a differential digital elevation approach was applied. Although the differences depended on the zone of the test area and they changed along the monitoring period, the erosion rate could be catalogued as very low. The dual-frequency receiver satisfied the vertical centimetric precision limits for high accurate Digital Elevation Model (DEM), making it a reliable and accurate option to validate erosion studies in small areas.Research highlights: The results have allowed the characterization of multi-annual spatial redistribution of the topsoil at local scale, being of great help to design future prevention actions for the “tillage erosion” in olive grove environments. However, more tests are needed to guarantee the feasibility of low-cost receivers.Center for Advanced Studies in Earth Sciences, RNM282 Research Group (Junta de Andalucía), PAIUJA 2019/2

Is GNSS real-time positioning a reliable option to validate erosion studies at olive grove environments?

Aim of study: Soil degradation in agricultural areas is a widespread problem. In this framework, a data validation methodology is presented, including a study of the spatial resolution of Global Navigation Satellite System (GNSS) measurements, the calculation of erosion/deposition models, and the contribution of dual frequency and low-cost single frequency GNSS receivers.Area of study: A test olive grove in SE Spain.Material and methods: The study is based on three observation campaigns, between 2016 and 2018, using different GNSS receivers and working modes. The comparison between different surveys provide the volumetric variation over the analyzed period.Main results: Considering the dual-frequency receiver, there was no statistically significant difference between the means and the variances from 1.5 m and from 4.5 m data resolution at the 0.05 significance level. In order to estimate vertical differences from successive GNSS campaigns a differential digital elevation approach was applied. Although the differences depended on the zone of the test area and they changed along the monitoring period, the erosion rate could be catalogued as very low. The dual-frequency receiver satisfied the vertical centimetric precision limits for high accurate Digital Elevation Model (DEM), making it a reliable and accurate option to validate erosion studies in small areas.Research highlights: The results have allowed the characterization of multi-annual spatial redistribution of the topsoil at local scale, being of great help to design future prevention actions for the “tillage erosion” in olive grove environments. However, more tests are needed to guarantee the feasibility of low-cost receivers

European traditional tomatoes galore: a result of farmers' selection of a few diversity-rich loci

A comprehensive collection of 1254 tomato accessions, corresponding to European traditional and modern varieties, early domesticated varieties, and wild relatives, was analyzed by genotyping by sequencing. A continuous genetic gradient between the traditional and modern varieties was observed. European traditional tomatoes displayed very low genetic diversity, with only 298 polymorphic loci (95% threshold) out of 64 943 total variants. European traditional tomatoes could be classified into several genetic groups. Two main clusters consisting of Spanish and Italian accessions showed higher genetic diversity than the remaining varieties, suggesting that these regions might be independent secondary centers of diversity with a different history. Other varieties seem to be the result of a more recent complex pattern of migrations and hybridizations among the European regions. Several polymorphic loci were associated in a genome-wide association study with fruit morphological traits in the European traditional collection. The corresponding alleles were found to contribute to the distinctive phenotypic characteristic of the genetic varietal groups. The few highly polymorphic loci associated with morphological traits in an otherwise a low-diversity population suggests a history of balancing selection, in which tomato farmers likely maintained the morphological variation by inadvertently applying a high selective pressure within different varietal types