1696 research outputs found
Sort by
The Utility of Immuno-Nutritional Scores in Patients with Testicular Germ Cell Tumors
No full textBackground: Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP) is an accessible score that is easily reproducible from routine laboratory testing while also reflecting patients’ immune-nutritional status. Along with other immuno-nutritional scores, such as the Prognostic Nutrition Index (PNI), HALP has been associated with a number of clinical and pathological features. The goal of our study was to evaluate the prognostic utility of HALP and PNI scores in testicular germ cell cancer (GCT) patients. Methods: This case-only study included 203 testicular GCT patients who were classified according to the disease stage and HALP and PNI cut-offs. Complete blood count and albumin concentration were routinely determined. Results: The values of HALP and PNI significantly differed among different clinical stages (p < 0.05). Moreover, they clearly exposed a significantly higher risk of advanced clinical stage development for those testicular GCT patients with lower values of HALP and PNI (p < 0.05). Finally, lower score levels were associated with larger tumor size (p < 0.05). Conclusion: Our investigation could provide evidence that specific immune-nutritional scores can help distinguish individuals diagnosed with testicular GCT who are more likely to be identified with advanced disease stages
Influence of bone substitute PerOssal® on bone marrrow mesenchymal stem cells
No full textINTRODUCTION: PerOssal® is biologically degradable and osteoconductive bone substitute consisting of
nanocrystalline hydroxyapatite (51.5 %) and calcium sulfate (48.5 %) [1]. It is used for bone defect treatments as a
synthetic carrier for antibiotics suitable for infected areas. Since the effect of PerOssal® has not been investigated so far
in combination with mesenchymal stem cells (MSC) for bone tissue regeneration, we aimed to explore in vitro whether
this material can support growth and osteogenesis of MSC from bone marrow (BM-MSC).
Materials and Methods: BM-MSC were isolated from BM mononuclear cell fraction of human healthy donors and
cultivated in standard conditions. One pellet of PerOssal® was dissolved in 10 ml of Phosphate Buffered Saline and
added to cells in different ratios. Viability of BM-MSC was assessed by MTT test [2] after one, five and seven days.
Migration capacity of BM-MSC was followed by both scratch assay and transwell system [3], while osteogenic potential
was investigated by histochemical staining after induced osteogenic differentiation [4].
RESULTS AND DISCUSSION: Initial experiments showed that BM-MSC adhere to PerOssal® surface. Considering that
culture media induced decomposition of PerOssal® which aggravated functional evaluation of attached BM-MSC , our
further in vitro studies were directed on testing the effects of different PerOssal® dilutions on BM-MSC functional
properties. Our results demonstrated that at all dilutions tested PerOssal® didn’t affect viability of BM-MSC in a shortterm
treatment, while in higher doses it decreased cell viability at day 7. At the same time point, morphology of BMMSC
was changed with high dose of PerOssal®. On the other side, at lower doses PerOssal® stimulated migration of BMMSC
as demonstrated by both scratch and transwell assays. As for the analyses of BM-MSC osteogenic differentiation,
stimulatory effect on early osteogenesis was noticed for lower PerOssal® doses, opposite to decreased BM-MSC
osteogenesis observed when higher doses were applied.
CONCLUSIONS: These data imply that osteoinductive effect of PerOssal® related to BM-MSC recruitment likely
considers later phases of material resorption corresponding to its lower concentrations. For potential use as a
biomaterial for cell therapy in tissue engineering, PerOssal® should be applied in lower doses.Supplementary Issue, ExcellMater Conference 2024 Abstract
Retained adipogenic potential and proinflammatory features of bone marrow mesenchymal stromal cells of metastatic breast cancer patients
No full textObjective(s): The skeleton is one of the most common metastatic sites for breast cancer (BC), and bone marrow is prone
to be inhabited by disseminated BC cells (BCCs). BCC osteotropism and colonization of the metastatic bone marrow
niche lead to pain, inflammatory osteolytic bone lesions, fractures, and decreased patient survival rate. Previous data
reported that BCCs colonized the bone marrow adipose tissue (BMAT) compartment where adipocytes supported BCC
chemoresistance. Mesenchymal stromal/stem cells (MSCs) participate in the creation of pre-metastatic and metastatic
niches for disseminated BCCs, but there is insufficient evidence on the role of adipogenic progenitors within MSCs and
bone marrow adipocytes in metastatic BC. In this study, we explored BMAT content and profile of MSCs related to
altered bone marrow niche in metastatic BC patients.
Method(s): Femoral bone marrow specimens were obtained from metastatic BC patients (n=10) and female patients
with hip arthrosis (n=6, control group) undergoing orthopedic surgery. Specimens were used for BMAT extraction, and
expansion of MSCs form BC patients (BC-MSCs) or MSCs from hip arthrosis patients (non-BC-MSCs). Ex vivo cellular
assays were performed at 3% oxygen. Cell (immuno)phenotype and secretome were determined by flow cytometry,
multiplex immunoassays, and immunofluorescent microscopy.
Result(s): Results showed the BMAT content was significantly lower in the bone marrow of BC than of arthrosis patients
(n=7, p=0.16). However, after induction of adipogenic differentiation, expanded BC-MSCs demonstrated similar
adipogenic capacity as observed in non-BC-MSCs. Moreover, alkaline phosphatase activity was stronger in BC-MSCs than
in non-BC-MSCs upon osteogenesis induction. BC-MSCs expressed a set of in vitro MSC antigens (CD44, CD90, CD105
and CD73), while being deficient for hematopoietic antigens (CD45, CD34 and CD235). When compared to non-BC
MSCs, BC-MSCs showed stronger expression of Vimentin and α-SMA. Analyses of cytokines produced in 24-hour
conditioned media showed higher production of IFNγ, IFNα2, TNFα, IL-18 in BM-MSCs than in non-BC-MSCs. Also,
BC-MSCs produced higher levels of VEGF, SCF, G-CSF and PDGFα, but lower levels of Ang2 and FGFb than non-BC
MSCs. Yet, conditioned media from both BC-MSCs and non-BC-MSCs only moderately changed the viability of BC cell
lines (MCF-7 and MDA-MB-231).
Conclusion(s): These results showed that a pro-inflammatory cancer-associated state can be associated with the
preserved adipogenic potential of bone marrow MSCs in metastatic BC. Further investigation will reveal the molecular
background of adipogenesis in metastatic BC-educated MSCs and its significance for BCCs in the bone marrow niche to
improve a development of therapies to manage skeletal pathologies in metastatic BC
Left atrial and left ventricular positive and negative remodeling after catheter ablation of atrial fibrillation
No full textIntroduction
Atrial fibrillation (AF) is associated with negative remodeling of left atrium (LA) and in later stages of diseases with negative remodeling of left ventricle (LV). Can radiofrequency ablation (RFA) of pulmonary veins cure AF and retain progression of arrhythmia?
Purpose
This study evaluated positive and negative remodeling of LA and LV after RFA of pulmonary veins and a 7-year follow-up. The patients were divided into 4 groups on the basis of Pulmonary Vein Isolation Outcome Degree (PVIOD 1-4), a new measure for the efficacy of catheter ablation of AF.
Methods
One hundred seventeen patients with symptomatic drug-refractory paroxysmal and persistent AF were treated with RFA. At baseline and after a 7 years of follow-up, 2-dimensional echocardiography was performed to assess LA diameter, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF).
Results
After a 7-year follow-up 32.5% patients with successful single RFA of AF (PVIOD 1) showed significant positive LA and LV remodeling: LA diameter 39.3±0.6 vs 36.5±0.6 mm, p=0.0007; LVEDD 53.1±0.6 vs 50.9±0.7 mm, p=0.008; LVESD 34.7±0.8 vs 32.0±0.1 mm, p=0.005 and LVEF 56.8±0.8 vs 62.1±1.1 %, p=0.000008. In 29.1% of patients with success after multiple procedures (PVIOD 2) occurred significant reverse LA remodeling: LA diameter 41.9±0.7 vs 40.2±0.6 mm, p=0.04. Clinical success (PVIOD 3) after RFA was defined as a significant reduction in the number and duration of AF episodes with or without previously ineffective antiarrhythmic drugs (AAD) class I and III. In 14.5% of subjects with long-term clinical success (PVIOD 3 and baseline LA diameter 43.2±1.0 mm) remodeling of LA and LV was not occurred. In 23.9% of patients with procedural and clinical failure after RFA (PVIOD 4) long-term follow-up showed significant negative remodeling of LA and LV: LA diameter 44.7±0.7 vs 47.4±0.7 mm, p=0.006; LVEDD 52.8±0.9 vs 57.1±0.6 mm, p=0.0006; LVESD 36.5±1.1 vs 40.7±1.2 mm, p=0.006 and LVEF 50.7±1.7 vs 43.8±1.8 %, p=0.004.
Conclusions
Single successful RFA of pulmonary veins in early stage of AF with normal LA diameter cure arrhythmia, which was proved with LA and LV positive remodeling after a 7-year follow-up. With increase of LA diameter, the success of RFA decrease. The multiple procedures slow the progression of AF, but are less effective because of long periods of time between them. Clinical success and role of AAD therapy are also important in AF management. If AF is not treated with RFA properly on time it becomes progressive disease.ESC Congress 2024 30 August – 02 September London, UK Abstract Supplemen
Preliminary characterization of putative tick cement protein PA107 – implications for possible applications in biomedicine
No full textIn addition to enabling blood meal uptake, by inhibiting blood coagulation, immune response
activation and inflammation, tick salivary proteins (TSPs) are also the key components of tick
cement. It forms a plug that surrounds tick mouth parts and protects them from host defense
molecules, keeps a feeding wound free of microbes, and provides a firm attachment to host skin
during feeding. A tick-unique protein present across tick genera - PA107 is a putative cement protein,
transcribed in tick salivary glands at the start of a feeding. Herein, a detailed in silico analysis of its
primary and tertiary structure was performed, along with the immunogenicity assessment by using
the recombinant protein derived from Ixodes ricinus species, medically the most important tick in
Europe. The screening of the primary structure placed it to the glycine-rich protein family, revealing
in parallel an overlapping 15mer at the C-terminus and borderline homology to non-tick proteins with
antimicrobial activity. The analysis of tertiary structure revealed a high degree of intrinsic disorder
for monomeric PA107, in contrast to highly ordered structures for different oligomeric states that
might correlate with the putative role in the tick cement formation process. In vitro findings showed
the lack of humoral response induction in experimentally infested rats and persons bitten by the
I. ricinus ticks. Controllable (de)polymerization, strength, and non-immunogenic features of tick
cement and its components (i.e. PA107) could be used for development of new tissue glues, with
better performances and lower toxicity compared with currently used
Diagnostic psychiatric and somatic comorbidity in patients with depression in the Western Balkan countries
Get PDFIntroduction: This paper aims to examine the frequency and significance of diagnostic comorbidity of psychiatric disorders and somatic diseases in a sample of patients with depression as well as present current psychopharmacological treatment of the patients in the sample. Methods The subjects in this study sample were 489 patients from the four Western Balkan countries with current primary diagnosis of major depression according to ICD 10. Comorbid psychiatric disorders and non-psychiatric illnesses were noted according to ICD 10 criteria during the diagnostic interview and analysed later. Additionally, the pharmacological treatment (existing and newly introduced) for each patient was noted and analysed later. Results At least one comorbid psychiatric disorder was present in 72.5% of patients. The most frequent were anxiety disorders (53.6%), specifically generalized anxiety disorder (20.2%); non-organic sleep disorders (50.7%), specifically insomnia (48.4%); and sexual dysfunctions (21.4%), specifically lack of sexual desire (20.2%). Comorbidity with any non-psychiatric illness was present in 80.3% of patients. The most frequent were circulatory system diseases (55.9%), specifically hypertension (45.9%); endocrine, nutritional and metabolic disorders (51.3%), specifically hyperlipidaemia (24.0%); and other non-psychiatric disorders (60.7%), specifically low back pain (22.7%). All patients received pharmacological treatment with different medications. Most patients received monotherapy or combination therapy of antidepressants, anxiolytics, antipsychotics and antiepileptics. The most frequently used antidepressants were escitalopram, sertraline, and duloxetine. The most frequently used anxiolytics were alprazolam and diazepam, the most used antiepileptic was pregabalin, and the most used antipsychotics were olanzapine, quetiapine, and aripiprazole. Conclusion The results of the study confirm the results of previous research studies about the high prevalence of psychiatric and non-psychiatric comorbidities in patients with depression that were conducted in the past. It would be important if future studies could prove the importance of those comorbidities on clinical severity, choice of treatment, and its outcome in patients with depression
Effect of coordination mode of thiosemicarbazone on the biological activities of its Ru(II)-benzene complexes: Biomolecular interactions and anticancer activity via ROS-mediated mitochondrial apoptosis
No full textRu(II)-benzene complexes (P1 and P2) were synthesized using a thiosemicarbazone ligand (L1) in two different coordination modes, monodentate S and bidentate N,S, through carefully adjusted reaction conditions. Comprehensive characterization of the complexes was achieved through single crystal X-ray diffraction, revealing a piano-stool geometry around the Ru(II) ion. To evaluate the binding capabilities of the complexes towards CT DNA and BSA, UV–Vis and/or hydrodynamic methods were utilized. Docking studies further validated the intercalative binding mode with DNA, in agreement with the experimental findings, and identified specific BSA amino acids involved in the binding interactions. Based on the results of binding studies, cytotoxicity of the ligand and complexes was appraised in various cancer and normal cell lines alongside the commercial pharmaceutics. Complexes P1 and P2 displayed a promising activity against MDA-MB-231 [IC50 = 5.11 (P1) and 3.48 μM (P2)] and PANC-1 [IC50 = 7.20 (P1) and 4.85 μM (P2)] cancer cells; with the bidentate system (P2) exhibiting a higher activity than its monodentate congener P1, although both of them showed superior activity than the reference drugs. Various bioassays including Western blot analysis revealed the mode of cell death to be apoptosis, which was further concluded to be via the ROS-mediated mitochondrial signaling pathway
Long Time No Hear, Magnificent Wohlfahrtia! Morphological and Molecular Evidence of Almost Forgotten Flesh Fly in Serbia and Western Balkans
Get PDFThe “beautiful viviparous fly”, Wohlfahrtia magnifica, may have a magnificent appearance due to its striking morphology; however, it is a potentially deadly agent of obligate traumatic myiasis in humans and animals, with a serious impact on welfare and economics. The fly is found across the Palearctic realm, including the Western Balkan region, with reports from former Yugoslavian countries from the first half of the 20th century. In this paper, a recent case of wohlfahrtiosis recorded in Northern Serbia is evidenced using morphological and molecular techniques. Larvae were collected from two adult sheep with severe hoof myiasis and two young sheep with genital and interdigital myiasis. Morphological identification was performed for adults bred from the infested vulva and third-stage larvae (L3) collected from the hoof wounds, supported with barcoding sequences of the COI gene obtained from larval pairs from the hoof wounds of older and the genitalia of younger sheep. W. magnifica was identified according to the appearance of male fly terminalia and the morphology of L3, which was confirmed after the comparison of representative sequences of the COI gene (deposited in GenBank™ under accession numbers MT027108–MT027114) to those available in GenBank™. This finding represents the first reported case of wohlfahrtiosis in the Western Balkans in 80 years, highlighting the need to re-inform relevant stakeholders to achieve adequate disease control
Interactions between mesenchymal stem cells and macrophage in stress erythropoiesis: roles for nitric oxide and purinergic signalling
No full textBackground:
Stress erythropoiesis (SE) is a comprehensive term that describes an increase in erythroid output in response to anemic stress.
It occurs within a specialized microenvironment where interactions between macrophages and mesenchymal stem cells (MSC)
play a crucial role in maintaining this environment. The key molecules implicated in SE are erythropoietin and
glucocorticoids. Extracellular adenosine triphosphate ATP (eATP) and nitric oxide (NO) have emerged as critical signals of
stress responses, but their crosstalk during SE remains elusive. Acting as a stress-associated molecule with paracrine/autocrine effects, eATP activates P2X7 receptor (P2X7R) that responds to high eATP levels, or rapidly converts to
adenosine by CD39 and CD73.The Abstract Book of European Hematology Association’s 29th Annual Congress - EHA2024 Congress, June 13-16 2024, Madri