High fat-fed diabetic mice present with profound alterations of the osteocyte network

Diabetes mellitus is considered to be an independent risk factor for bone fragility fractures. Reductions in bone mass, observed only with type 1 diabetes mellitus, as well as modifications of bone microarchitectures and tissue material properties are landmarks of diabetes-related bone alterations. An interesting feature observed in type 2 diabetes mellitus (T2DM) is the augmented concentration in circulating sclerostin. This observation prompts us to hypothesize that modifications of osteocyte network and perilacunar mineralization occur in T2DM. As such, the aims of the present study were to ascertain by quantitative backscattered electron imaging, confocal microscopy and image analysis, modifications of perilacunar tissue mineral density, osteocyte morphology and osteocyte network topology in a mouse model of high fat-induced type 2 diabetes. As compared with lean control animals, diabetic mice exhibited a significant 48% decrease in perilacunar mineralization heterogeneity although mean perilacunar mineralization was unchanged. Furthermore, in diabetic animals, osteocyte volume was significantly augmented by 34% with no change in the overall number of dendrite processes. Finally, the network topology was profoundly modified in diabetic mice with increases in the mean node degree, mean node volume and hub numbers whilst the mean link length was reduced. Overall, it appeared that in diabetic animals, the dendritic network exhibited features of a scale-free network as opposed to the single-scale characteristic observed in lean controls. However, it is important to ascertain whether diabetic patients exhibit such modifications of the osteocyte network and whether anti-diabetic drugs could restore normal osteocyte and network parameters, thereby improving bone quality and protecting against fragility fractures.     

在体骨髓原位造血细胞间纳米通道的扫描电子显微镜(SEM)证据

 目的  探讨在体骨髓细胞之间是否存在细胞间纳米通道(intercellular nanotubes)。方法  利用扫描电子显微镜(scanning electron microscope,SEM)在体原位观察C57BL/6小鼠骨髓中细胞间纳米通道的分布、形态以及可能的形成机制。结果  骨髓造血细胞之间存在纳米通道结构。SEM显示该结构在骨髓组织中散在分布,位于骨髓内血窦内、外侧。骨髓造血细胞间纳米通道的管径粗细不均,平均长度为5.85 μm (1.58~18.54 μm),平均直径为364 nm (202~541 nm),还可见一些小颗粒状物质黏附在纳米通道表面。此外,小鼠骨髓造血细胞可能通过伸出突起的形式形成细胞间纳米通道。结论  本研究首次为小鼠骨髓造血细胞之间存在细胞间纳米通道提供了形态学证据。     

Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1⁺), myeloid-committed progenitors (CD11b⁺, Gr-1⁺), and lymphoid-committed progenitors (CD45⁺, CD3e⁺). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1⁺ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b⁺ and Gr-1⁺ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45⁺ and CD3e⁺ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.     

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan

Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in the absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of gellan gum and 20% kappa-carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6 h.     

Impact of serum uric acid on subclinical myocardial injury in general population

Background and aimsHyperuricemia is widely thought as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the relation of serum uric acid (sUA) and subclinical myocardial injury (SCeMI) remains unclear. We hypothesize that sUA is associated with subclinical myocardial injury.Methods and resultsA total of 5880 adult individuals (57.9 ± 13.0 years, 54.23% women) without known cardiovascular disease from National Health and Nutrition Examination Survey (NHANES) III were included. Determined by Cardiac Infarction Injury Score (CIIS) from 12-lead electrocardiogram, SCeMI was defined by CIIS ≥10 units. The relationship between sUA and SCeMI was analyzed by using logistic regression models and the smooth curve fitting. Subgroup analyses were conducted. After adjusting for potential confounding variables, the smooth curve fitting revealed a non-linear relationship between sUA level and SCeMI. When sUA was above the inflection point 266.5 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 15%. In women group, when sUA>340.3 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 71%, but no significant correlation was observed in men group.ConclusionsOur findings confirm that sUA is an independent risk factor for subclinical myocardial injury after adjusting for potential confounding variables, and existence of such an association in women only, which require more random control trials to confirm the strategy of cardiovascular disease prevention based on sUA reduction in female.     

Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review

BackgroundFew data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF).MethodsWe performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies’ report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale.ResultsA total of 11 studies were eligible for final analysis (n = 1481 patients with HF). The studies were segregated into 3 groups: (1) the evaluation of patients presenting to the emergency department with dyspnea, (2) the evaluation of patients presenting to the HF clinic for follow-up, and (3) the evaluation of hospitalized patients with acutely decompensated HF or undergoing right heart catheterization. US parameters included IJV height, IJV diameter, IJV diameter ratio, IJV cross-sectional area, respiratory compressibility index, and compression compressibility index.ConclusionsThe findings of this systematic review suggest a significant role for ultrasound interrogation of the IJV in evaluation of patients in the emergency department presenting with dyspnea, in the outpatient clinic for poor clinical outcomes in HF, and in determining the timing of discharge for patients admitted with acutely decompensated HF. Further studies are warranted for testing the reliability of the reported ultrasound indices.