scholarly journals A Versatile Macromer-Based Glycosaminoglycan (sHA3) Decorated Biomaterial for Pro-Osteogenic Scavenging of Wnt Antagonists

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1037
Author(s):  
Mathis Gronbach ◽  
Franziska Mitrach ◽  
Stephanie Möller ◽  
Sandra Rother ◽  
Sabrina Friebe ◽  
...  
Keyword(s):  
Serum Levels ◽  
Bone Defects ◽  
High Serum ◽  
Qualitative And Quantitative Analysis ◽  
Negative Effects ◽  
Bone Defect Healing ◽  
2D System ◽  
Surface Decoration ◽  
The Impact ◽  
Regeneration Of Bone

High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin. Film surfaces representing scaffold implants were cross-copolymerized from three-armed biodegradable macromers and glycidylmethacrylate and covalently decorated with various polyetheramine linkers. The impact of linker properties (size, branching) and density on sHA3 functionalization efficiency and scavenging capacities for sclerostin was tested. The copolymerized 2D system allowed for finding an optimal, cytocompatible formulation for sHA3 functionalization. On these optimized sHA3 decorated films, we showed efficient scavenging of Wnt antagonists DKK1 and sclerostin, whereas Wnt agonist Wnt3a remained in the medium of differentiating SaOS-2 and hMSC. Consequently, qualitative and quantitative analysis of hydroxyapatite staining as a measure for osteogenic differentiation revealed superior mineralization on sHA3 materials. In conclusion, we showed how our versatile material platform enables us to efficiently scavenge and inactivate Wnt antagonists from the osteogenic micromilieu. We consider this a promising approach to reduce the negative effects of Wnt antagonists in regeneration of bone defects via sHA3 decorated macromer based macroporous implants.

scholarly journals POS0329 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS: PATHOGENETIC ROLE OF GUT MICROBIOME, CYTOKINES AND ADIPOKINES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 392.1-392
Author(s):  
E. Pigatto ◽  
M. Schiesaro ◽  
M. Caputo ◽  
M. Beggio ◽  
P. Galozzi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Gut Microbiome ◽  
Serum Levels ◽  
High Serum ◽  
Healthy Population ◽  
Gastrointestinal Involvement ◽  
Degrading Bacteria ◽  
Gi Symptoms ◽  
Low Levels ◽  
The Impact

Background:Gastrointestinal (GI) involvement is very common in patients with Systemic Sclerosis (SSc). The pathophysiology of GI manifestations has not yet been defined. Cell-mediated immunological reactions appear to lead to endothelial damage resulting in fibrosis. The risk of developing malnutrition reinforces the need to better understand GI pathophysiology in these patients.Objectives:The study aimed to evaluate GI symptoms (GIT 2.0) and malnutrition status (MUST) and to determine specific bacterial changes in gut microbiome by investigating the possible presence of positive hot spots in bacterial species in SSc patients and their potential role in the disease progression. We also evaluated serum levels of adipokines and cytokines involved in the pathogenesis of SSc and their role, in addition to gut microbiome, in predicting the onset of GI involvement and malnutrition in SSc patients.Methods:We enrolled 25 scleroderma patients (EULAR/ACR 2013 criteria). UCLA-SCTC GIT 2.0 questionnaire to evaluate GI symptoms and MUST to investigate the risk of malnutrition were used. Gut microbiome was analyzed and the samples were subjected to extraction for the 16S rRNA gene (Earth Microbiome Project and the NIH-Human Microbiome Project). The microbiome was investigated at phenotypic and genotypic level. Serum levels of cytokines and adipokines (adiponectin and leptin) were evaluated by ELISA.Results:79.9% of patients had GERD and 63.5% abdominal distension at GIT 2.0 questionnaires. 48% of patients had moderate risk of malnutrition (MUST=2) and 12% had high risk (MUST=3). Gut microbioma: 19 patients (76%) had low similarity and 11 (44%) low diversity compared to the healthy population. The prevailing enterotypes of gut microbiome was Bacteroides (80%) and Prevotella (20%). The genotypic evaluation showed a reduced concentration of: gluten-digesting (Lactobacillus); lactose-digesting (Faecalibacterium); vitamin K-producing (Enterococcus, Desulfovibrio and Veillonella); acetaldehyde-degrading bacteria. 24 patients (96%) showed a reduction in bacteria devoted to maintaining weight control (Bifidobacterium and Ruminococcus). The patients had an altered intestinal permeability with less mucolytic bacteria (Bacteroides) and reduced production of LPS (Enterobacter and Escherichia). Low levels of butyrate (Eubacterium and Clostridium), acetate and propionate were found for SCFA-producing bacteria. Potentially pathogenic bacteria were also investigated: Salmonella was found in 14 (56%), Klebsiella in 9 (36%) and Enterococcus Faecalis in 3 (12%) patients. 11 (44%) patients had elevated serum levels of IL10 and IL12; 4 (16%) had high value of leptin. Correlation was found in patients who had a reduced concentration of gluten-digesting bacteria and MUST. Elevated MUST was correlated with serological increase in IL17A and IFN-α. Serum levels of IL12 and IL10 were found to correlate with specific bacteria alterations: high concentration of acetaldehyde-producing bacteria and low levels of acetaldehyde-degrade bacteria (also correlated with high serum levels of IL6), mucolytic bacteria and producers of hydrogen sulphide, acetate and propionate. Finally, reduced levels of mucolytic bacteria and acetate producing bacteria correlated with high serum leptin levels.Conclusion:The relationship between the gut microbiome and SSc seems to be multifactorial. In our study genotypic changes of gut microbioma might play a role in damaging the permeability of the mucosa and increasing risk of malnutrition. The evaluation of gut microbiome and cytokine profile is probably going to be of value in the follow-up of SSc. However, further studies are needed to clarify the impact of GI dysbiosis on the immune system in SSc.References:[1]Patrone V. et al. Gut microbiota profile in systemic sclerosis patients with and without clinical evidence of gastrointestinal involvement, Sci Rep. 2017; 7: 14874Disclosure of Interests:None declared

Serum 2-Hydroxyglutarate Level Is a Prognostic Marker in Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1433-1433
Author(s):  
Jing-Han Wang ◽  
Wen-Lian Chen ◽  
Tian-Lu Chen ◽  
Yong-Mei Zhu ◽  
Wei-Na Zhang ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Conflicts Of Interest ◽  
Methylation Status ◽  
Gene Mutations ◽  
Serum Levels ◽  
Hematologic Malignancies ◽  
High Serum ◽  
Independent Prognostic Marker ◽  
High Level ◽  
The Impact

Abstract Abstract 1433 BACKGROUND High levels of 2-HG in serum were found among AML cases with IDH1/IDH2 mutations. However, the impact of 2-HG levels on biological characteristics and clinical outcomes has not been systematically evaluated in a large cohort of AML patients. METHODS Serum 2-HG levels in 699 patients with hematologic malignancies, including 405 AML patients, were measured by GC-TOFMS. Clinical prognostic power of 2-HG and genetic risk factors associated with 2-HG were also evaluated in AML patients. RESULTS Among all patients with hematopoietic malignancies investigated, high serum 2-HG levels were observed only in AML group. 64 out of 405 (15.8%) AML patients displayed aberrantly higher levels (7.14±2.11μg/ml) of 2-HG. Compared to cases with normal 2-HG (3.65±1.02μg/ml), these patients showed a higher prevalence in AML-M0/M1 subtypes, a closer correlation with mutated IDH1/2 genes, a distinct gene expression profile and an aberrant DNA methylation status in bone marrow blasts. Additionally, the patients with high 2-HG were associated with higher serum levels of α-ketoglutarate (α-KG) and glutamate, suggesting presence of impaired metabolic pathway involved in the biosynthesis of 2-HG. Univariate and multivariate analyses indicate that high level of 2-HG is among the most significant negative indicators for complete remission (CR) rate, overall survival (OS) and event-free survival (EFS) either in all AML cases or in cases with cytogenetically normal AML (CN-AML). CONCLUSIONS Serum 2-HG is an independent prognostic marker in AML. Patients with high 2-HG had significantly higher frequency of IDH1/IDH2 gene mutations and unfavorable prognosis compared to those with normal 2-HG. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Volume-Regulated Anion Channel in Glioblastoma

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 307 ◽  
Author(s):  
Martino Caramia ◽  
Luigi Sforna ◽  
Fabio Franciolini ◽  
Luigi Catacuzzeno
Keyword(s):  
Cell Migration ◽  
Cell Volume ◽  
Signal Transduction Pathway ◽  
Anion Channel ◽  
Serum Levels ◽  
High Serum ◽  
Human Brain Tumor ◽  
Original Cell ◽  
The Impact

Malignancy of glioblastoma multiforme (GBM), the most common and aggressive form of human brain tumor, strongly depends on its enhanced cell invasion and death evasion which make surgery and accompanying therapies highly ineffective. Several ion channels that regulate membrane potential, cytosolic Ca2+ concentration and cell volume in GBM cells play significant roles in sustaining these processes. Among them, the volume-regulated anion channel (VRAC), which mediates the swelling-activated chloride current (IClswell) and is highly expressed in GBM cells, arguably plays a major role. VRAC is primarily involved in reestablishing the original cell volume that may be lost under several physiopathological conditions, but also in sustaining the shape and cell volume changes needed for cell migration and proliferation. While experimentally VRAC is activated by exposing cells to hypotonic solutions that cause the increase of cell volume, in vivo it is thought to be controlled by several different stimuli and modulators. In this review we focus on our recent work showing that two conditions normally occurring in pathological GBM tissues, namely high serum levels and severe hypoxia, were both able to activate VRAC, and their activation was found to promote cell migration and resistance to cell death, both features enhancing GBM malignancy. Also, the fact that the signal transduction pathway leading to VRAC activation appears to involve GBM specific intracellular components, such as diacylglicerol kinase and phosphatidic acid, reportedly not involved in the activation of VRAC in healthy tissues, is a relevant finding. Based on these observations and the impact of VRAC in the physiopathology of GBM, targeting this channel or its intracellular regulators may represent an effective strategy to contrast this lethal tumor.

scholarly journals Resistin and Cardiac Arrest—A Prospective Study

2019 ◽  
Vol 9 (1) ◽  
pp. 57
Author(s):  
Raluca M. Tat ◽  
Adela Golea ◽  
Rodica Rahaian ◽  
Ştefan C. Vesa ◽  
Daniela Ionescu
Keyword(s):  
Cardiac Arrest ◽  
Ischemia Reperfusion ◽  
Univariate Analysis ◽  
Laboratory Data ◽  
Early Death ◽  
Serum Levels ◽  
High Serum ◽  
Cardiovascular Comorbidities ◽  
Biological Variables ◽  
The Impact

The systemic response to ischemia-reperfusion that occurs after a cardiac arrest (CA) followed by the return of spontaneous circulation leads to endothelial toxicity and cytokine production, both responsible for the subsequent occurrence of severe cardiocirculatory dysfunction and early death. Resistin is emerging as a biomarker of proinflammatory status and myocardial ischemic injury and as a mediator of endothelial dysfunction. The study aimed to analyze the possible associations between several clinical and biological variables and the serum levels of resistin in CA survivors. Forty patients with out-of-hospital resuscitated CA, were enrolled in the study. Demographic, clinical and laboratory data (including serum resistin measurements at admission and at 6, 12, 24, 48 and 72 h) were recorded. For resistin, we calculated the area under the curve (AUC) using the trapezoidal method with measurements from 0 to 12 h, 0 to 24 h, 0 to 48 h and 0 to 72 h. Fifteen (37.5%) patients died in the first 72 h after CA. Cardiovascular comorbidities were present in 65% of patients. The majority of patients had post-CA shock (29 (72.5%)). Resistin serum levels rose in the first 12–24 h and decreased in the next 48–72 h. In univariate analysis, advanced age, longer duration of resuscitation, high sequential organ failure assessment score, high lactate levels, presence of cardiovascular comorbidities and the post-CA shock were associated with higher resistin levels. In multivariate analysis, post-CA shock or cardiovascular comorbidities were independently associated with higher AUCs for resistin for 0–12 h and 0–24 h. The only identified variable to independently predict higher AUCs for resistin for 0–48 h and 0–72 h was the presence of post-CA shock. Our data demonstrate strong independent correlation between high serum resistin levels, cardiac comorbidities and post-CA shock. The impact of the post-CA shock on serum concentration of resistin was greater than that of cardiac comorbidities.

The More Control, the Better?

2014 ◽  
Vol 26 (2) ◽  
pp. 81-91 ◽  
Author(s):  
Jeeyun Oh ◽  
Mun-Young Chung ◽  
Sangyong Han
Keyword(s):  
Mixed Design ◽  
Negative Effects ◽  
Story Structure ◽  
Content Type ◽  
High User ◽  
User Control ◽  
Rigorous Research ◽  
Control Versus ◽  
The Media ◽  
The Impact

Despite of the popularity of interactive movie trailers, rigorous research on one of the most apparent features of these interfaces – the level of user control – has been scarce. This study explored the effects of user control on users’ immersion and enjoyment of the movie trailers, moderated by the content type. We conducted a 2 (high user control versus low user control) × 2 (drama film trailer versus documentary film trailer) mixed-design factorial experiment. The results showed that the level of user control over movie trailer interfaces decreased users’ immersion when the trailer had an element of traditional story structure, such as a drama film trailer. Participants in the high user control condition answered that they were less fascinated with, absorbed in, focused on, mentally involved with, and emotionally affected by the movie trailer than participants in the low user control condition only with the drama movie trailer. The negative effects of user control on the level of immersion for the drama trailer translated into users’ enjoyment. The impact of user control over interfaces on immersion and enjoyment varies depending on the nature of the media content, which suggests a possible trade-off between the level of user control and entertainment outcomes.

Benign ovarian fibroma with ascites and high serum levels of CA125: a case report

2007 ◽  
Vol 67 (05) ◽  
Author(s):  
N Shabani ◽  
T Puchner ◽  
H Schütze ◽  
U Jeschke ◽  
I Mylonas ◽  
...  
Keyword(s):  
Case Report ◽  
Serum Levels ◽  
High Serum ◽  
Ovarian Fibroma

Monetary policy and the effect of the transfer of oil prices to inflation

2020 ◽  
pp. 41-50
Author(s):  
Ph. S. Kartaev ◽  
I. D. Medvedev
Keyword(s):  
Monetary Policy ◽  
Inflation Targeting ◽  
Dynamic Models ◽  
Oil Prices ◽  
Oil Price ◽  
Oil Price Shocks ◽  
Negative Effects ◽  
Price Shocks ◽  
Policy Regime ◽  
The Impact

The paper examines the impact of oil price shocks on inflation, as well as the impact of the choice of the monetary policy regime on the strength of this influence. We used dynamic models on panel data for the countries of the world for the period from 2000 to 2017. It is shown that mainly the impact of changes in oil prices on inflation is carried out through the channel of exchange rate. The paper demonstrates the influence of the transition to inflation targeting on the nature of the relationship between oil price shocks and inflation. This effect is asymmetrical: during periods of rising oil prices, inflation targeting reduces the effect of the transfer of oil prices, limiting negative effects of shock. During periods of decline in oil prices, this monetary policy regime, in contrast, contributes to a stronger transfer, helping to reduce inflation.

Retrospective analysis of the resilience of Russian regions as socio-economic systems

2019 ◽  
pp. 46-64 ◽  
Author(s):  
Vladimir V. Klimanov ◽  
Sofiya М. Kazakova ◽  
Anna A. Mikhaylova
Keyword(s):  
Panel Data ◽  
Economic Systems ◽  
Financial Indicators ◽  
Russian Regions ◽  
Integral Index ◽  
Negative Effects ◽  
Economic Resilience ◽  
Correlation Dependence ◽  
The Impact ◽  
The Relationship

The article examines the impact of various socio-economic and financial indicators on the resilience of Russian regions. For each region, the integral index of resilience is calculated, and its correlation dependence with the selected indicators is revealed. The study confirms the relationship between fiscal resilience and socio-economic resilience of the regions. The analysis of panel data for 75 regions from 2007 to 2016 shows that there are significant differences in the dynamics of indicators in different periods. In particular, the degree of exposure to the negative effects of the crises of 2008—2009 and 2014—2015 in non-resilient regions is higher than in resilient ones.

Factors Influencing Academic Stress on Students of University of Economics and Business - Vietnam National University

2020 ◽  
Vol 36 (3) ◽  
Author(s):  
Nham Phong Tuan ◽  
Nguyen Ngoc Quy ◽  
Nguyen Thi Thanh Huyen ◽  
Hong Tra My ◽  
Tran Nhu Phu
Keyword(s):  
Academic Stress ◽  
Stress Factors ◽  
Negative Effects ◽  
Cross Sectional ◽  
Stress Scale ◽  
Perceptions And Attitudes ◽  
National University ◽  
Questionnaire Surveys ◽  
The University ◽  
The Impact

The objective of this study is to investigate the impact of seven factors causing academic stress on students of University of Economics and Business - Vietnam National University: Lack of leisure time, Academic performance, Fear of failure, Academic overload, Finances, Competition between students, Relationships with university faculty. Based on the results of a practical survey of 185 students who are attending any courses at the University of Economics and Business - Vietnam National University, the study assesses the impact of stress factors on students. The thesis focuses on clarifying the concept of "stress" and the stress level of students, while pointing out its negative effects on students. This study includes two cross-sectional questionnaire surveys. The first survey uses a set of 16 questions to assess students’ perceptions and attitudes based on an instrument to measure academic stress - Educational Stress Scale for Adolescents (ESSA). The second survey aims to test internal consistency, the robustness of the previously established 7-factor structure. Henceforth, the model was brought back and used qualitatively, combined with Cronbach’s Alpha measurement test and EFA discovery factor analysis. This study was conducted from October 2019 to December 2019. From these practical analyzes, several proposals were made for the society, the school and the students themselves.

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