Functionalization of Polycaprolactone Electrospun Osteoplastic Scaffolds with Fluorapatite and Hydroxyapatite Nanoparticles: Biocompatibility Comparison of Human Versus Mouse Mesenchymal Stem Cells

A capability for effective tissue reparation is a living requirement for all multicellular organisms. Bone exits as a precisely orchestrated balance of bioactivities of bone forming osteoblasts and bone resorbing osteoclasts. The main feature of osteoblasts is their capability to produce massive extracellular matrix enriched with calcium phosphate minerals. Hydroxyapatite and its composites represent the most common form of bone mineral providing mechanical strength and significant osteoinductive properties. Herein, hydroxyapatite and fluorapatite functionalized composite scaffolds based on electrospun polycaprolactone have been successfully fabricated. Physicochemical properties, biocompatibility and osteoinductivity of generated matrices have been validated. Both the hydroxyapatite and fluorapatite containing polycaprolactone composite scaffolds demonstrated good biocompatibility towards mesenchymal stem cells. Moreover, the presence of both hydroxyapatite and fluorapatite nanoparticles increased scaffolds’ wettability. Furthermore, incorporation of fluorapatite nanoparticles enhanced the ability of the composite scaffolds to interact and support the mesenchymal stem cells attachment to their surfaces as compared to hydroxyapatite enriched composite scaffolds. The study of osteoinductive properties showed the capacity of fluorapatite and hydroxyapatite containing composite scaffolds to potentiate the stimulation of early stages of mesenchymal stem cells’ osteoblast differentiation. Therefore, polycaprolactone based composite scaffolds functionalized with fluorapatite nanoparticles generates a promising platform for future bone tissue engineering applications.     

Bis(2,2′-bipyridil)Copper(II) Chloride Complex: Tyrosinase Biomimetic Catalyst or Redox Mediator?

In this article, construction of amperometric sensor(s) based on screen-printed carbon electrodes covered by thin layers of two types of carbon nanomaterials serving as amplifiers, and containing [Cu(bipy)₂Cl]Cl∙5H₂O complex is reported. Their performance and biomimetic activity towards two selected neurotransmitters (dopamine and serotonin) was studied mainly using flow injection analysis (FIA). The important parameters of FIA such as working potential, flow rate, and pH were optimized. The mechanism of the catalytic activity is explained and experimentally confirmed. It reveals that presence of hydrogen peroxide plays a crucial role which leads to answer the title question: can presented complex really be considered as a tyrosinase biomimetic catalyst or only as a redox mediator?     

Temporal associations between morningness/eveningness,problematic social media use,psychological distress and daytime sleepiness: Mediated roles of sleep quality and insomnia among young adults

The extant literature has suggested relationships between an individual's chronotype (in relation to morningness/eveningness) and several outcomes, including addictive disorders, psychological distress and daytime sleepiness. Moreover, sleep quality has been proposed to be a mediator in the aforementioned relationships. Consequently, the aim of the present study was to investigate the complex relationship between morningness/eveningness, problematic social media use, psychological distress and daytime sleepiness, with the potential mediators of sleep quality and insomnia. All participants (N = 1,791 [30.1% males]; mean age = 27.2 years, SD = 10.1) completed a battery of psychometric scales, including a reduced version of the Morningness‐Eveningness Questionnaire (at baseline), the Pittsburgh Sleep Quality Index and Insomnia Severity Index (1 month after baseline assessment), the Bergen Social Media Addiction Scale, the Hospital Anxiety and Depression Scale, and the Epworth Sleepiness Scale (2 months after baseline assessment). The impacts of morningness‐eveningness on problematic social media use, anxiety, depression and daytime sleepiness were found in the mediation models. Furthermore, the mediated effects of insomnia and sleep quality were observed. The present study's results emphasize the importance of promoting healthy sleep habits and sleep hygiene behaviours, and that of early detection of sleep problems among individuals who have the eveningness chronotype, because this would significantly improve their health outcomes.     

Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies

AimDiabetic nephropathy (DN) is one of the worst complications of diabetes. Despite a growing number of DN metabolite profiling studies, most studies are suffering from inconsistency in their findings. The main goal of this meta-analysis was to reach to a consensus panel of significantly dysregulated metabolites as potential biomarkers in DN.Data synthesisTo identify the significant dysregulated metabolites, meta-analysis was performed by “vote-counting rank” and “robust rank aggregation” strategies. Bioinformatics analyses were performed to identify the most affected genes and pathways. Among 44 selected studies consisting of 98 metabolite profiles, 17 metabolites (9 up-regulated and 8 down-regulated metabolites), were identified as significant ones by both the meta-analysis strategies (p-value<0.05 and OR>2 or <0.5) and selected as DN metabolite meta-signature. Furthermore, enrichment analyses confirmed the involvement of various effective biological pathways in DN pathogenesis, such as urea cycle, TCA cycle, glycolysis, and amino acid metabolisms. Finally, by performing a meta-analysis over existing time-course studies in DN, the results indicated that lactic acid, hippuric acid, allantoin (in urine), and glutamine (in blood), are the topmost non-invasive early diagnostic biomarkers.ConclusionThe identified metabolites are potentially involved in diabetic nephropathy pathogenesis and could be considered as biomarkers or drug targets in the disease.Prospero registration numberCRD42020197697.     

Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines

The NOTCH ligand, JAG2, was found to be overexpressed in malignant plasma cells from multiple myeloma (MM) patients and cell lines but not in nonmalignant plasma cells from tonsils, bone marrow from healthy individuals, or patients with other malignancies. In addition, JAG2 overexpression was detected in 5 of 5 patients with monoclonal gammopathy of undetermined significance (MGUS), an early phase of myeloma disease progression. This overexpression appears to be a consequence of hypomethylation of the JAG2 promoter in malignant plasma cells. An in vitro coculture assay was used to demonstrate that JAG2 induced the secretion of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) in stromal cells. Further, the induction of IL-6 secretion was blocked in vitro by interference with anti-Notch-1 monoclonal antibodies raised against the binding sequence of Notch-1 with JAG2. Taken together, these results indicate that JAG2 overexpression may be an early event in the pathogenesis of multiple myeloma involving IL-6 production.     

Bedside score predicting retained common bile duct stone in acute biliary pancreatitis

BACKGROUND Retained common bile duct(CBD) stone after an acute episode of biliary pancreatitis is of paramount importance since stone extraction is mandatory.AIM To generate a simple non-invasive score to predict the presence of CBD stone in patients with biliary pancreatitis.METHODS We performed a retrospective study including patients with a diagnosis of biliary pancreatitis. One hundred and fifty-four patients were included. Thirty-three patients(21.5%) were diagnosed with CBD stone by endoscopic ultrasound(US).RESULTS In univariate analysis, age(OR: 1.048, P = 0.0004), aspartate transaminase(OR:1.002, P = 0.0015), alkaline phosphatase(OR: 1.005, P = 0.0005), gamma-glutamyl transferase(OR: 1.003, P = 0.0002) and CBD width by US(OR: 1.187, P = 0.0445)were associated with CBD stone. In multivariate analysis, three parameters were identified to predict CBD stone;age(OR: 1.062, P = 0.0005), gamma-glutamyl transferase level(OR: 1.003, P = 0.0003) and dilated CBD(OR: 3.685, P = 0.027),with area under the curve of 0.8433. We developed a diagnostic score that included the three significant parameters on multivariate analysis, with assignment of weights for each variable according to the co-efficient estimate. A score that ranges from 51.28 to 73.7 has a very high specificity(90%-100%) for CBD stones, while a low score that ranges from 9.16 to 41.04 has a high sensitivity(82%-100%). By performing internal validation, the negative predictive value of the low score group was 93%.CONCLUSION We recommend incorporating this score as an aid for stratifying patients with acute biliary pancreatitis into low or high probability for the presence of CBD stone.     

Rapid detection of the factor XIII Val34Leu (163 G-->T) polymorphism by real-time PCR using fluorescence resonance energy transfer detection and melting curve analysis.

The Val34Leu polymorphism in the A subunit of blood coagulation factor XIII (FXIII-A) is located in the activation peptide, just three amino acids upstream of the thrombin cleavage site. The Val-->Leu replacement accelerates the rate of the proteolytic activation of FXIII and it seems to provide protection against myocardial infarction. Methods available for the assessment of the FXIII-A Val34Leu polymorphism are rather time-consuming, laborious and not easily applicable for large-scale studies. In this study a new method based on real-time PCR with fluorescence resonance energy transfer (FRET) detection and melting curve analysis was developed. The rapid, simple method was adapted to the widely used real-time PCR instrument, LightCycler (Roche Diagnostics). The results showed 100% coincidence with those obtained by the traditional PCR-restriction fragment length polymorphism (RFLP) assay and fluorescent DNA sequencing. Using this method, an allele frequency of 24.2% was obtained (n=113), which well agrees with the allele frequency obtained by PCR-RFLP on a different group of the same ethnic Hungarian population (25.9%).