Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone ...homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have been considered and described to clarify the evidence of this link. The main goal of this review is to underline as deregulated miRNAs in osteoporosis may have specific roles in the development of bone metastases. The review showed that several circulating osteoporotic miRNAs could facilitate tumor progression and bone-metastasis formation in several tumor types, i.e., breast cancer, prostate cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, and multiple myeloma. In detail, serum up-regulation of pro-osteoporotic miRNAs, as well as serum down-regulation of anti-osteoporotic miRNAs are common features of all these tumors and are able to promote bone metastasis. These results are of key importance and could help researcher and clinicians to establish new therapeutic strategies connected with deregulation of circulating miRNAs and able to interfere with pathogenic processes of osteoporosis, tumor progressions, and bone-metastasis formation.
Aim
Chylothorax is a rare but life‐threatening condition in newborns. Octreotide, a somatostatin analogue, is widely used as a therapeutic option in neonates with congenital and acquired chylothorax, ...but its therapeutic role has not been clarified yet.
Methods
We performed a systematic review to assess the efficacy and safety of octreotide in the treatment of congenital and acquired chylothorax in newborns. Comprehensive research, updated till 31 October 2017, was performed by searching in PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases using the MeSH terms ‘octreotide’ and ‘chylothorax’. Both term and preterm newborns with congenital or acquired chylothorax treated with octreotide within the 30th day of life were included. Octreotide treatment was considered effective if a progressive reduction/ceasing in drained chylous effusion occurred.
Results
A total of 39 articles were included. Octreotide was effective in 47% of patients, with a slight but not significant difference between congenital (30/57; 53.3%) and acquired (9/27; 33.3%) chylothorax (P = 0.10). Marked variation in octreotide regimen was observed. The most common therapeutic scheme was intravenous infusion at a starting dose of 1 μg/kg/h, gradually increasing to 10 μg/kg/h according to the therapeutic response. Side effects were reported in 12 of 84 patients (14.3%). Only case reports were included in this review due to the lack of randomised controlled trials.
Conclusion
Octreotide is a relatively effective and safe treatment option in neonates with chylothorax, especially for the congenital forms.
Body fat distribution, usually measured using waist-to-hip ratio (WHR), is an important contributor to cardiometabolic disease independent of body mass index (BMI). Whether mechanisms that increase ...WHR via lower gluteofemoral (hip) or via higher abdominal (waist) fat distribution affect cardiometabolic risk is unknown.
To identify genetic variants associated with higher WHR specifically via lower gluteofemoral or higher abdominal fat distribution and estimate their association with cardiometabolic risk.
Genome-wide association studies (GWAS) for WHR combined data from the UK Biobank cohort and summary statistics from previous GWAS (data collection: 2006-2018). Specific polygenic scores for higher WHR via lower gluteofemoral or via higher abdominal fat distribution were derived using WHR-associated genetic variants showing specific association with hip or waist circumference. Associations of polygenic scores with outcomes were estimated in 3 population-based cohorts, a case-cohort study, and summary statistics from 6 GWAS (data collection: 1991-2018).
More than 2.4 million common genetic variants (GWAS); polygenic scores for higher WHR (follow-up analyses).
BMI-adjusted WHR and unadjusted WHR (GWAS); compartmental fat mass measured by dual-energy x-ray absorptiometry, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, type 2 diabetes, and coronary disease risk (follow-up analyses).
Among 452 302 UK Biobank participants of European ancestry, the mean (SD) age was 57 (8) years and the mean (SD) WHR was 0.87 (0.09). In genome-wide analyses, 202 independent genetic variants were associated with higher BMI-adjusted WHR (n = 660 648) and unadjusted WHR (n = 663 598). In dual-energy x-ray absorptiometry analyses (n = 18 330), the hip- and waist-specific polygenic scores for higher WHR were specifically associated with lower gluteofemoral and higher abdominal fat, respectively. In follow-up analyses (n = 636 607), both polygenic scores were associated with higher blood pressure and triglyceride levels and higher risk of diabetes (waist-specific score: odds ratio OR, 1.57 95% CI, 1.34-1.83, absolute risk increase per 1000 participant-years ARI, 4.4 95% CI, 2.7-6.5, P < .001; hip-specific score: OR, 2.54 95% CI, 2.17-2.96, ARI, 12.0 95% CI, 9.1-15.3, P < .001) and coronary disease (waist-specific score: OR, 1.60 95% CI, 1.39-1.84, ARI, 2.3 95% CI, 1.5-3.3, P < .001; hip-specific score: OR, 1.76 95% CI, 1.53-2.02, ARI, 3.0 95% CI, 2.1-4.0, P < .001), per 1-SD increase in BMI-adjusted WHR.
Distinct genetic mechanisms may be linked to gluteofemoral and abdominal fat distribution that are the basis for the calculation of the WHR. These findings may improve risk assessment and treatment of diabetes and coronary disease.
A triphasic scaffold (TPS) for the regeneration of the bone-ligament interface was fabricated combining a 3D fiber deposited polycaprolactone structure and a polylactic co-glycolic acid electrospun. ...The scaffold presented a gradient of physical and mechanical properties which elicited different biological responses from human mesenchymal stem cells. Biological test were performed on the whole TPS and on scaffolds comprised of each single part of the TPS, considered as the controls. The TPS showed an increase of the metabolic activity with culturing time that seemed to be an average of the controls at each time point. The importance of differentiation media for bone and ligament regeneration was further investigated. Metabolic activity analysis on the different areas of the TPS showed a similar trend after 7 days in both differentiation media. Total alkaline phosphatase (ALP) activity analysis showed a statistically higher activity of the TPS in mineralization medium compared to the controls. A different glycosaminoglycans amount between the TPS and its controls was detected, displaying a similar trend with respect to ALP activity. Results clearly indicated that the integration of electrospinning and additive manufacturing represents a promising approach for the fabrication of scaffolds for the regeneration of tissue interfaces, such as the bone-to-ligament one, because it allows mimicking the structural environment combining different biomaterials at different scales.
A generic chemical transformation may often be achieved under various synthetic conditions. However, for any specific reagents, only one or a few among the reported synthetic protocols may be ...successful. For example, Michael β-addition reactions may proceed under different choices of solvent (e.g., hydrophobic, aprotic polar, protic) and catalyst (e.g., Brønsted acid, Lewis acid, Lewis base, etc.). Chemoinformatics methods could be efficiently used to establish a relationship between the reagent structures and the required reaction conditions, which would allow synthetic chemists to waste less time and resources in trying out various protocols in search for the appropriate one. In order to address this problem, a number of 2-classes classification models have been built on a set of 198 Michael reactions retrieved from literature. Trained models discriminate between processes that are compatible and respectively processes not feasible under a specific reaction condition option (feasible or not with a Lewis acid catalyst, feasible or not in hydrophobic solvent, etc.). Eight distinct models were built to decide the compatibility of a Michael addition process with each considered reaction condition option, while a ninth model was aimed to predict whether the assumed Michael addition is feasible at all. Different machine-learning methods (Support Vector Machine, Naive Bayes, and Random Forest) in combination with different types of descriptors (ISIDA fragments issued from Condensed Graphs of Reactions, MOLMAP, Electronic Effect Descriptors, and Chemistry Development Kit computed descriptors) have been used. Models have good predictive performance in 3-fold cross-validation done three times: balanced accuracy varies from 0.7 to 1. Developed models are available for the users at http://infochim.u-strasbg.fr/webserv/VSEngine.html. Eventually, these were challenged to predict feasibility conditions for ∼50 novel Michael reactions from the eNovalys database (originally from patent literature).
We report on the integration of inkjet-printed graphene with a CMOS micro-electro-mechanical-system (MEMS) microhotplate for humidity sensing. The graphene ink is produced via ultrasonic assisted ...liquid phase exfoliation in isopropyl alcohol (IPA) using polyvinyl pyrrolidone (PVP) polymer as the stabilizer. We formulate inks with different graphene concentrations, which are then deposited through inkjet printing over predefined interdigitated gold electrodes on a CMOS microhotplate. The graphene flakes form a percolating network to render the resultant graphene-PVP thin film conductive, which varies in presence of humidity due to swelling of the hygroscopic PVP host. When the sensors are exposed to relative humidity ranging from 10-80%, we observe significant changes in resistance with increasing sensitivity from the amount of graphene in the inks. Our sensors show excellent repeatability and stability, over a period of several weeks. The location specific deposition of functional graphene ink onto a low cost CMOS platform has the potential for high volume, economic manufacturing and application as a new generation of miniature, low power humidity sensors for the internet of things.
Hyperbolic Metamaterials are artificially engineered materials whose optical properties can be specifically tailored to manifest an extremely high level of anisotropy. Due to this remarkable ...anisotropy they represent a unique opportunity to realize effective bulk meta-structure with extraordinary optical properties in the visible range. A simultaneous dielectric singularity in the in plane permittivity, with respect to the propagation direction, has to lead to a complete sign inversion of the same permittivity for that specific visible frequency. Such a drastic phase change has been theoretically highlighted in the past as the major challenge to be overcome in order to unlock many remarkable optical properties not present artificial optical systems. In this paper we experimentally demonstrate the realization of a metal-dielectric multilayer structure showing an inversion point of coexisting anisotropies at a specified wavelength in the visible range, rising from the particular design and fabrication process. Theoretical models and numerical simulations are in very good agreement with experimental data. Ellipsometrical experiments and optical modeling demonstrate the drastic type I/type II transition. Supercollimation effect has been achieved at the inversion point of the coexisting extreme anisotropies, whereas at the epsilon near zero and pole frequency the perfect lens behavior has been observed.
We analyze the thermalization properties and the validity of the eigenstate thermalization hypothesis in a generic class of quantum Hamiltonians where the quench parameter explicitly breaks a Z ...sub(2) symmetry. Natural realizations of such systems are given by random matrices expressed in a block form where the terms responsible for the quench dynamics are the off-diagonal blocks. Our analysis examines both dense and sparse random matrix realizations of the Hamiltonians and the observables. Sparse random matrices may be associated with local quantum Hamiltonians and they show a different spread of the observables on the energy eigenstates with respect to the dense ones. In particular, the numerical data seem to support the existence of rare states, i.e., states where the observables take expectation values that are different compared to the typical ones sampled by the microcanonical distribution. In the case of sparse random matrices, we also extract the finite-size behavior of two different time scales associated with the thermalization process.
Reactive oxygen species like hydrogen peroxide (H2O2) are produced endogenously and may participate in intra- and extracellular signaling, including modulation of angiotensin II responses. In the ...present study, we investigated the effects of chronic subcutaneous (sc) administration of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) on arterial pressure, autonomic modulation of arterial pressure, hypothalamic expression of AT1 receptors and neuroinflammatory markers and fluid balance in 2-kidney, 1clip (2K1C) renovascular hypertensive rats.
Male Holtzman rats with a clip occluding partially the left renal artery and chronic sc injections of ATZ were used.
Subcutaneous injections of ATZ (600 mg/kg of body weight/day) for 9 days in 2K1C rats reduced arterial pressure (137 ± 8, vs. saline: 182 ± 8 mmHg). ATZ also reduced the sympathetic modulation and enhanced the parasympathetic modulation of pulse interval, reducing the sympatho-vagal balance. Additionally, ATZ reduced mRNA expression for interleukins 6 and IL-1β, tumor necrosis factor-α, AT1 receptor (0.77 ± 0.06, vs. saline: 1.47 ± 0.26 fold change), NOX 2 (0.85 ± 0.13, vs. saline: 1.75 ± 0.15 fold change) and the marker of microglial activation, CD 11 (0.47 ± 0.07, vs. saline, 1.34 ± 0.15 fold change) in the hypothalamus of 2K1C rats. Daily water and food intake and renal excretion were only slightly modified by ATZ.
The results suggest that the increase of endogenous H2O2 availability with chronic treatment with ATZ had an anti-hypertensive effect in 2K1C hypertensive rats. This effect depends on decreased activity of sympathetic pressor mechanisms and mRNA expression of AT1 receptors and neuroinflammatory markers possibly due to reduced angiotensin II action.
Representative schematic of the main finds of this study showing the effects of the injection of ATZ decreasing proinflammatory cytokines, AT1 receptor expression, and microglia activation in the hypothalamus of hypertensive rats leading to a decrease in cardiac and vasomotor sympathetic modulation that contribute to the decrease in hypertension in the 2K1C hypertensive animals. Display omitted
PDF
