Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, ...performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)/receptor for AGEs (RAGE), fibrotic Wnt/β-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, markers of fibrosis (collagen deposition, fibronectin, TGF-β1, and Wnt/β-catenin pathway), hypertrophy of the kidney and/or heart were analysed. At the end of study, diabetic rats showed higher levels of urinary sKlotho, AGEs and sRAGE and lower serum sKlotho compared with controls without differences in the renal Klotho expression. A significant positive correlation was found between urinary sKlotho and AGEs and urinary albumin/creatinine ratio (uACR). Fibrosis and RAGE levels were significantly higher in the heart without differences in the kidney of diabetic rats compared to controls. The results also suggest the increase in sKlotho and sRAGE excretion may be due to polyuria in the diabetic rats.
To establish a new procedure for 3D geometric reconstruction of the human cornea to obtain a solid model that represents a personalized and in vivo morphology of both the anterior and posterior ...corneal surfaces. This model is later analyzed to obtain geometric variables enabling the characterization of the corneal geometry and establishing a new clinical diagnostic criterion in order to distinguish between healthy corneas and corneas with keratoconus.
The method for the geometric reconstruction of the cornea consists of the following steps: capture and preprocessing of the spatial point clouds provided by the Sirius topographer that represent both anterior and posterior corneal surfaces, reconstruction of the corneal geometric surfaces and generation of the solid model. Later, geometric variables are extracted from the model obtained and statistically analyzed to detect deformations of the cornea.
The variables that achieved the best results in the diagnosis of keratoconus were anterior corneal surface area (ROC area: 0.847, p<0.000, std. error: 0.038, 95% CI: 0.777 to 0.925), posterior corneal surface area (ROC area: 0.807, p<0.000, std. error: 0.042, 95% CI: 0,726 to 0,889), anterior apex deviation (ROC area: 0.735, p<0.000, std. error: 0.053, 95% CI: 0.630 to 0.840) and posterior apex deviation (ROC area: 0.891, p<0.000, std. error: 0.039, 95% CI: 0.8146 to 0.9672).
Geometric modeling enables accurate characterization of the human cornea. Also, from a clinical point of view, the procedure described has established a new approach for the study of eye-related diseases.
The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for ...creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus.
We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months.
Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval CI, 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months.
Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).
Phosphorus is a vital element for life found in most foods as a natural component, but it is also one of the most used preservatives added during food processing. High serum phosphorus contributes to ...develop vascular calcification in chronic kidney disease; however, it is not clear its effect in a population without kidney damage. The objective of this in vivo and in vitro study was to investigate the effect of high phosphorus exposure on the aortic and serum levels of miR-145 and its effect on vascular smooth muscle cell (VSMCs) changes towards less contractile phenotypes. The study was performed in aortas and serum from rats fed standard and high-phosphorus diets, and in VSMCs exposed to different concentrations of phosphorus. In addition, miR-145 silencing and overexpression experiments were carried out. In vivo results showed that in rats with normal renal function fed a high P diet, a significant increase in serum phosphorus was observed which was associated to a significant decrease in the aortic α-actin expression which paralleled the decrease in aortic and serum miR-145 levels, with no changes in the osteogenic markers. In vitro results using VSMCs corroborated the in vivo findings. High phosphorus first reduced miR-145, and afterwards α-actin expression. The miR-145 overexpression significantly increased α-actin expression and partially prevented the increase in calcium content. These results suggest that miR-145 could be an early biomarker of vascular calcification, which could give information about the initiation of the transdifferentiation process in VSMCs.
In the present article, we describe a study of antitumor activity in breast cell lines using silver nanoparticles (Ag NPs) synthesized by a microbiological method. These Ag NPs were tested for their ...antitumor activity against MCF7 and T47D cancer cells and MCF10-A normal breast cell line. We analyzed cell viability, apoptosis induction, and endocytosis activity of those cell lines and we observed that the effects of the biosynthesized Ag NPs were directly related with the endocytosis activity. Moreover, Ag NPs had higher inhibition efficacy in tumor lines than in normal lines of breast cells, which is due to the higher endocytic activity of tumor cells compared to normal cells. In this way, we demonstrate that biosynthesized Ag NPs can be an alternative for the treatment of tumors.
The rapid advances of 3D techniques for the structural determination of proteins and the development of numerous computational methods and strategies have led to identifying highly active compounds ...in computer drug design. Molecular docking is a method widely used in high-throughput virtual screening campaigns to filter potential ligands targeted to proteins. A great variety of docking programs are currently available, which differ in the algorithms and approaches used to predict the binding mode and the affinity of the ligand. All programs heavily rely on scoring functions to accurately predict ligand binding affinity, and despite differences in performance, none of these docking programs is preferable to the others. To overcome this problem, consensus scoring methods improve the outcome of virtual screening by averaging the rank or score of individual molecules obtained from different docking programs. The successful application of consensus docking in high-throughput virtual screening highlights the need to optimize the predictive power of molecular docking methods.
Aim
Metacommunity ecology is a vibrant area of research that has received increased attention in recent years, since it provides a framework to assess the underlying dispersal‐ and niche‐based ...processes that create non‐random and ecologically meaningful patterns in species assemblages across the landscape. Here we set out to test for the role of dispersal limitation, species sorting and shared effects in the assembly of pond macrophyte metacommunities across an extensive area within the Iberian Plateau, and to identify which traits, environmental variables and spatial scales are driving local community structure.
Location
North‐western Spain (Iberian Plateau).
Taxon
Pond macrophytes.
Methods
We established a novel combination of robust methods capable of identifying the processes and most important landscape scales involved in the assembly of communities. We used metacommunity assembly modelling and multivariate multi‐scale codependence analysis (mMCA) to first estimate the relative importance of spatial and environmental effects on community structure, and then to identify significant trait–environment relationships and spatial scales.
Results
Analyses showed that the greatest effects were seen for the spatial and mixed spatial and niche‐based scenarios, particularly among wind‐dispersed species. Thus, dispersal limitation interfered with species sorting in determining assemblage structure by hindering species’ tracking of local environmental conditions. After accounting for this, the metacommunity assembly model revealed that species’ traits were involved in determining abundance structure. mMCA identified the main trait–environment relationships (and spatial scales) as fruit size‐nutrient status (~300 km) and growth form‐mean pond depth (~250 km).
Main conclusions
Our study suggests that dispersal limitation acted in concert with species sorting to influence the community assembly processes underlying selection for particular traits in functional niche space. Accordingly, we emphasize the need to go beyond the traditional taxonomic‐based analyses of community composition and the predominant thinking of considering spatial and environmental processes as two alternative and mutually exclusive scenarios of community assembly.
Temperature of tissues and organs is one of the first parameters affected by physiological and pathological processes, such as metabolic activity, acute trauma, or infection‐induced inflammation. ...Therefore, the onset and development of these processes can be detected by monitoring deviations from basal temperature. To accomplish this, minimally invasive, reliable, and accurate measurement of the absolute temperature of internal organs is required. Luminescence nanothermometry is the ideal technology for meeting these requirements. Although this technique has lately undergone remarkable developments, its reliability is being questioned due to spectral distortions caused by biological tissues. In this work, how the use of bright Ag2S nanoparticles featuring temperature‐dependent fluorescence lifetime enables reliable and accurate measurement of the absolute temperature of the liver in mice subjected to lipopolysaccharide‐induced inflammation is demonstrated. Beyond the remarkable thermal sensitivity (≈ 3% °C–1 around 37 °C) and thermal resolution obtained (smaller than 0.3 °C), the results included in this work set a blueprint for the development of new diagnostic procedures based on the use of intracorporeal temperature as a physiological indicator.
Lifetime‐based infrared luminescent nanothermometers are shown to be minimally affected by the effects of biological tissues on the propagation of photons. Real‐time and reliable thermal monitoring of the liver of a mouse subjected to lipopolysaccharide‐induced inflammation is achieved through the use of bright Ag2S nanoparticles. Remarkable thermal sensitivity (3% °C–1 around 37 °C) and thermal resolution (smaller than 0.3 °C) are obtained.
ABSTRACT
The Neptunian desert is a region in period-radius parameter space with very few Neptune-sized planets at short orbital periods. Amongst these, LTT 9779 b is the only known Neptune with a ...period shorter than 1 d to retain a significant H–He atmosphere. If the Neptune desert is the result of X-ray/EUV-driven photoevaporation, it is surprising that the atmosphere of LTT 9779 b survived the intense bombardment of high-energy photons from its young host star. However, the star has low measured rotational broadening, which points to the possibility of an anomalously slow spin period and hence a faint X-ray emission history that may have failed to evaporate the planet’s atmosphere. We observed LTT 9779 with XMM-Newton and measured an upper limit for its X-ray luminosity that is a factor of 15 lower than expected for its age. We also simulated the evaporation past of LTT 9779 b and found that the survival of its atmosphere to the present day is consistent with an unusually faint XUV irradiation history that matches both the X-ray and rotation velocity measurements. We conclude that the anomalously low X-ray irradiation of the one Neptune seen to survive in Neptunian desert supports the interpretation of the desert as primarily a result of photoevaporation.
ABSTRACT
We model the evaporation histories of the three planets around K2-136, a K-dwarf in the Hyades open cluster with an age of 700 Myr. The star hosts three transiting planets, with radii of ...1.0, 3.0, and 1.5 Earth radii, where the middle planet lies above the radius–period valley and the inner and outer planets are below. We use an XMM–Newton observation to measure the XUV radiation environment of the planets, finding that the X-ray activity of K2-136 is lower than predicted by models but typical of similar Hyades members. We estimate the internal structure of each planet, and model their evaporation histories using a range of structure and atmospheric escape formulations. While the precise X-ray irradiation history of the system may be uncertain, we exploit the fact that the three planets must have shared the same history. We find that the Earth-sized K2-136b is most likely rocky, with any primordial gaseous envelope being lost within a few Myr. The sub-Neptune, K2-136c, has an envelope contributing 1–1.7 per cent of its mass that is stable against evaporation thanks to the high mass of its rocky core, whilst the super-Earth, K2-136d, must have a mass at the upper end of the allowed range in order to retain any of its envelope. Our results are consistent with all three planets beginning as sub-Neptunes that have since been sculpted by atmospheric evaporation to their current states, stripping the envelope from planet b and removing most from planet d whilst preserving planet c above the radius-period valley.
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