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European Journal of Neurology Jan 2021To investigate changes in serum complements and their regulators in the pathogenesis of myasthenia gravis (MG).
OBJECTIVE
To investigate changes in serum complements and their regulators in the pathogenesis of myasthenia gravis (MG).
METHODS
Forty-four patients with acetylcholine receptor antibody-positive MG, as well as 20 patients with non-inflammatory neurological disorders were enrolled. Serum complements (C3, C4 and soluble C5b-9) and complement regulators (vitronectin, clusterin and properdin) were extensively analysed by enzyme-linked immunosorbent assay and their associations with clinical profiles of MG were examined.
RESULTS
Serum C3, C4 and clusterin levels were not significantly different between patients with MG and controls. The patients with MG had higher soluble C5b-9 (P = 0.09) and vitronectin (P = 0.001) levels than the controls; moreover, vitronectin levels decreased after treatment (P = 0.09). Serum properdin (P = 0.03) levels were lower in the patients with MG than in the controls, and negatively correlated with the MG Activities of Daily Living score (rs = -0.26, P = 0.09) and with the presence of bulbar palsy (P = 0.04).
CONCLUSION
Our results show that activation of complements and an altered complement network could contribute to the inflammatory pathogenesis of MG.
Topics: Activities of Daily Living; Autoantibodies; Complement System Proteins; Humans; Myasthenia Gravis; Receptors, Cholinergic
PubMed: 32889770
DOI: 10.1111/ene.14500 -
Molecules (Basel, Switzerland) Dec 2022In orthopedic, dental, and maxillofacial fields, joint prostheses, plates, and screws are widely used in the treatment of problems related to bone tissue. However, the...
In orthopedic, dental, and maxillofacial fields, joint prostheses, plates, and screws are widely used in the treatment of problems related to bone tissue. However, the use of these prosthetic systems is not free from complications: the fibrotic encapsulation of endosseous implants often prevents optimal integration of the prostheses with the surrounding bone. To overcome these issues, biomimetic titanium implants have been developed where synthetic peptides have been selectively grafted on titanium surfaces via Schiff base formation. We used the retro-inverted sequence (DHVPX) from [351-359] human Vitronectin and its dimer (D2HVP). Both protease-resistant peptides showed increased human osteoblast adhesion and proliferation, an augmented number of focal adhesions, and cellular spreading with respect to the control. D2HVP-grafted samples significantly enhance Secreted Phosphoprotein 1, Integrin Binding Sialoprotein, and Vitronectin gene expression vs. control. An estimation of peptide surface density was determined by Two-photon microscopy analysis on a silanized glass model surface labeled with a fluorescent analog.
Topics: Humans; Cell Adhesion; Vitronectin; Titanium; Peptide Hydrolases; Peptides; Osteoblasts; Endopeptidases; Surface Properties
PubMed: 36557865
DOI: 10.3390/molecules27248727 -
Calcified Tissue International Apr 2023Periostin, also known as osteoblast-specific factor 2, is a matricellular protein predominantly expressed at the periosteum of bone. During growth and development,...
Periostin, also known as osteoblast-specific factor 2, is a matricellular protein predominantly expressed at the periosteum of bone. During growth and development, periostin contributes to periosteal expansion by facilitating osteoblast differentiation and mineralization. Later in life, periosteal expansion provides an adaptive strategy to increase tissue strength without requiring substantial increase in bone mass. However, the function of periostin past skeletal maturity and during advanced aging is relatively unknown. The objective of this study was to examine the function of periostin in maintaining bone mass and tissue strength across different ages. In periostin null mice (Postn-/-), periosteal bone formation was significantly reduced in young (3 months) and adult mice (9 months). The lack of bone formation resulted in reduced bone mass and ultimate strength. Conversely, periosteal bone formation increased at advanced ages in 18-month-old Postn-/- mice. The increase in periosteal mineralization at advanced ages coincides with increased expression of vitronectin and osteopontin. Periosteal progenitors from Postn-/- mice displayed an increased capacity to mineralize when cultured on vitronectin, but not type-1 collagen. Altogether, these findings demonstrate the unique role of periostin in regulating periosteal bone formation at different ages and the potential for vitronectin to compensate in the absence of periostin.
Topics: Animals; Mice; Osteogenesis; Vitronectin; Periosteum; Mice, Knockout; Aging
PubMed: 36729140
DOI: 10.1007/s00223-023-01063-6 -
Animals : An Open Access Journal From... Aug 2019Vitronectin plays a role in the blood homeostasis and has been implicated in cell adhesion, migration, and proliferation. Vitronectin has a potential role affecting the...
Vitronectin plays a role in the blood homeostasis and has been implicated in cell adhesion, migration, and proliferation. Vitronectin has a potential role affecting the residual feed intake (RFI) or feeding efficiency in swine production. Its variations have not been reported in Chinese swine breeds. In this study, two regions of porcine vitronectin were analyzed using PCR and sequencing. The sequence analysis revealed thirteen nucleotide substitutions in region 1 (exon 2- exon 3) and three nucleotide substitutions in region 2 (exon 5- intron 5), which would result in five amino acid changes (p.Ala52Thr, p.Leu94Pro, p.Leu94Gln, p.Gln94Pro, and p.Glu126Gly). In region 1, c.156C/T, c.281A/T, and c.377A/G were the most common (at a total frequency of 49.3%, 31.3% and 31.9% respectively), whereas c.153C/T and c.180C/G were rare (at a total frequency of 1.39%). In region 2, c.597 + 12A/G was the most common (at a total frequency of 39.6%), followed by c.597 + 15A/G (at a total frequency of 31.3%) and c.459A/G (at a total frequency of 16.0%). There was a difference ( < 0.05) in variant frequencies between Chinese breeds and overseas breeds. These results indicate that the porcine vitronectin gene is polymorphic and suggest further analysis is required to see if the variation detected affects RFI or feed efficiency in swines.
PubMed: 31382414
DOI: 10.3390/ani9080520 -
Revista Da Associacao Medica Brasileira... 2023The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus.
OBJECTIVE
The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus.
METHODS
This study was conducted between September 2020 and December 2020 at the University of Health Sciences, Bursa Yuksek Ihtisas Research and Training Hospital, Department of Obstetrics and Gynecology. A total of 30 pregnant women with gestational diabetes mellitus and 60 healthy controls between 24 and 27/6 weeks of gestation were included. The inclusion criteria were as follows: being between 18 and 45 years old and 24-27/6 gestational weeks, having singleton pregnancy, diagnosed with gestational diabetes mellitus by using a two-step challenge test. The exclusion criteria of this study were as follows: chronic inflammatory or infectious disease, fasting blood glucose>126 mg/dL, intolerance to glucose tolerance testing, abnormal liver or kidney function tests, as well as pregnancy with pre-gestational diabetes history of adverse perinatal outcomes. Serum vitronectin and plasminogen activator inhibitor-1 levels were measured using the enzyme-linked immunosorbent assay method.
RESULTS
Vitronectin and plasminogen activator inhibitor-1 levels were higher in the gestational diabetes mellitus group compared with controls [91.85 (23.08) vs. 80.10 (39.18) ng/mL, for vitronectin and 6.50 (1.05) vs. 4.35(1.0) ng/mL, for plasminogen activator inhibitor-1 (for both p<0.001)]. vitronectin >84.7 ng/mL was found to predict gestational diabetes mellitus with a sensitivity of 70% and specificity of 63.3%. Moreover, vitronectin had a significant positive correlation with fasting blood glucose (r=0.476, p<0.001), postprandial blood glucose (r=0.489, p<0.001), HbA1c (r=0.713, p<0.001), and plasminogen activator inhibitor-1 (r=0.586, p<0.001).
CONCLUSION
This study revealed that second-trimester vitronectin and plasminogen activator inhibitor-1 are increased in gestational diabetes mellitus and vitronectin could be a candidate for the prediction of gestational diabetes mellitus.
Topics: Pregnancy; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Diabetes, Gestational; Vitronectin; Blood Glucose; Enzyme-Linked Immunosorbent Assay; Exercise Test
PubMed: 37729377
DOI: 10.1590/1806-9282.20230563 -
Cellular and Molecular Biology... Jan 2022Acute organophosphate poisoning kills tens of thousands of people annually around the world. These substances are widely used as insecticides in homes, industry, and...
The relationship of hs-CRP, vitronectin and NT-proBNP serum levels with the extent and severity of cardiac complications in patients with organophosphate pesticide poisoning.
Acute organophosphate poisoning kills tens of thousands of people annually around the world. These substances are widely used as insecticides in homes, industry, and agricultural environments. Due to the ease of access, they can cause accidental or intentional risks of exposure through the skin or respiratory contact. This study aimed to evaluate the serum levels of hs-CRP, Vitronectin, and NT-proBNP and their relationship with the extent and severity of cardiac complications in patients with organophosphate pesticide poisoning. In this descriptive-comparative study, 160 patients were studied with acute organophosphate poisoning. Also, for better comparison, 40 healthy individuals participated in this study. Diagnosis of organophosphate poisoning was based on clinical findings of serum butyrylcholinesterase levels. The hs-CRP measurement was performed by an autoanalyzer (Abbott, model Alcyon 300, USA) with the ELISA hs-CRP kit (The apDia Company, Belgium). Vitronectin (VN) measurements were performed by ELISA method and Glory science human VN kit with Catalog No: 11668. NT-ProBNP serum levels were analyzed by ProBNP assay kit (Roche, Germany) by ECLIA method using Elecsys 2010 Analyzer. The most important variables studied in this study were the electrical activity and conduction system of the heart, PR distance, QTC interval, and T-wave changes. In this study, most of the patients were women and girls (60.78%). The highest percentage of organophosphate poisoning was in the age group of 15-24 years (37.25%). In most cases (78.43%), poisoning was intentional or suicidal. Evaluation of electrophysiological abnormalities of the heart showed that 89 patients (55.62%) had long QTC interval (>450 msec), 43 cases (26.87%) had possible long QTC (431-450 msec), and 28 cases (17.5%) had normal QTC (<430 msec). Only 9.37% of cases (n = 15) showed an increase in P-R distance, which is characteristic of the first-degree ventricular atrial block. Sinus bradycardia occurred in 57 cases (35.62%) and sinus tachycardia in 43 cases (26.87%); in 60 cases (37.5%), the pulse rate was normal. Smooth T-wave changes were observed in 9.8% of patients and reverse T-wave was observed in 17.6%. A long T-wave was not reported in any case. In only two cases (1.25%) was grade 1 ventricular atrial block and grade 2 and 3 blocks were not observed. In general, there was a significant difference in the hs-CRP, vitronectin, and NT-proBNP serum levels between the patient and control groups in all studied variables. These parameters were also related to the extent and severity of the disease.
Topics: Adolescent; Adult; Arrhythmias, Cardiac; Biomarkers; Butyrylcholinesterase; C-Reactive Protein; Female; Heart Diseases; Humans; Insecticides; Male; Natriuretic Peptide, Brain; Organophosphate Poisoning; Organophosphates; Peptide Fragments; Pesticides; Vitronectin; Young Adult
PubMed: 35809283
DOI: 10.14715/cmb/2021.67.4.26 -
International Journal of Molecular... Jun 2021Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzyme-acetylgalactosamine-6-sulfate sulfatase (GALNS), and...
Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzyme-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroitin-6-sulfate in chondrocytes. Although improvements in the activity of daily living and endurance tests have been achieved with enzyme replacement therapy (ERT) with recombinant human GALNS, recovery of bone lesions and bone growth in MPS IVA has not been demonstrated to date. Moreover, no correlation has been described between therapeutic efficacy and urine levels of KS, which accumulates in MPS IVA patients. The objective of this study was to assess the validity of potential biomarkers proposed by other authors and to identify new biomarkers. To identify candidate biomarkers of this disease, we analyzed plasma samples from healthy controls (=6) and from untreated (=8) and ERT-treated (=5, sampled before and after treatment) MPS IVA patients using both qualitative and quantitative proteomics analyses. The qualitative proteomics approach analyzed the proteomic profile of the different study groups. In the quantitative analysis, we identified/quantified 215 proteins after comparing healthy control untreated, ERT-treated MPSIVA patients. We selected a group of proteins that were dysregulated in MPS IVA patients. We identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: fetuin-A, vitronectin, alpha-1antitrypsin, and clusterin. Further studies of cartilage and bone samples from MPS IVA patients will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.
Topics: Biomarkers; Case-Control Studies; Chondroitinsulfatases; Enzyme Replacement Therapy; Humans; Mucopolysaccharidosis IV; Proteome
PubMed: 34200496
DOI: 10.3390/ijms22116165 -
Nanotechnology, Science and Applications 2023Disorganisation of the extracellular matrix (ECM) is strongly connected to tumor progression. Even small-scale changes can significantly influence the adhesion and...
INTRODUCTION
Disorganisation of the extracellular matrix (ECM) is strongly connected to tumor progression. Even small-scale changes can significantly influence the adhesion and proliferation of cancer cells. Therefore, the use of biocompatible nanomaterials capable of supporting and partially replenishing degraded ECM might be essential to recover the niche after tumor resection. The objective of this study was to evaluate the influence of graphene, graphene oxide, fullerene, and diamond nanofilms on breast cancer and glioblastoma grade IV cell lines.
METHODS
Nanomaterials were characterized using SEM and TEM techniques; zeta potential analysis was also performed. Nanofilms of graphene, fullerene, and diamond nanoparticles were also characterized using AFM. The toxicity was tested on breast cancer MDA.MB.231 and glioblastoma grade IV U-87 MG cell lines, using LDH assay and by counting stained dead cells in bioprinted 3D models. The following parameters were analyzed: proliferation, adhesion to the nanofilm, and adhesion to particular ECM components covered with diamond nanoparticles.
RESULTS AND DISCUSSION
Our studies demonstrated that nanofilms of graphene and diamond nanoparticles are characterized by cell-specific toxicity. Those nanomaterials were non-toxic to MDA.MB.231 cells. After applying bioprinted 3D models, diamond nanoparticles were not toxic for both cell lines. Nanofilms made of diamond nanoparticles and graphene inhibit the proliferation of MDA.MB.231 cells after 48 and 72 hours. Increased adhesion on nanofilm made of diamond nanoparticles was only observed for MDA.MB.231 cells after 30 and 60 minutes from seeding the cells. However, analysis of adhesion to certain ECM components coated with diamond nanoparticles revealed enhanced adhesion to tenascin and vitronectin for both tested cell lines.
CONCLUSION
Our studies show that nanofilm made of diamond nanoparticles is a non-toxic and pro-adhesive nanomaterial that might stabilize and partially replenish the niche after breast tumor resection as it enhances the adhesion of breast cancer cells and inhibits their proliferation.
PubMed: 38111798
DOI: 10.2147/NSA.S439185 -
International Journal of Molecular... Dec 2021Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological... (Review)
Review
Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological and pathophysiological conditions and is controlled by a wide range of proangiogenic and antiangiogenic molecules. The plasminogen activator-plasmin system plays a major role in the extracellular matrix remodeling process necessary for angiogenesis. Urokinase/tissue-type plasminogen activators (uPA/tPA) convert plasminogen into the active enzyme plasmin, which in turn activates matrix metalloproteinases and degrades the extracellular matrix releasing growth factors and proangiogenic molecules such as the vascular endothelial growth factor (VEGF-A). The plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of uPA and tPA, thereby an inhibitor of pericellular proteolysis and intravascular fibrinolysis, respectively. Paradoxically, PAI-1, which is expressed by EC during angiogenesis, is elevated in several cancers and is found to promote angiogenesis by regulating plasmin-mediated proteolysis and by promoting cellular migration through vitronectin. The urokinase-type plasminogen activator receptor (uPAR) also induces EC cellular migration during angiogenesis via interacting with signaling partners. Understanding the molecular functions of the plasminogen activator plasmin system and targeting angiogenesis via blocking serine proteases or their interactions with other molecules is one of the major therapeutic strategies scientists have been attracted to in controlling tumor growth and other pathological conditions characterized by neovascularization.
Topics: Animals; Humans; Models, Biological; Neovascularization, Pathologic; Neovascularization, Physiologic; Plasminogen; Serine Proteases; Tissue Plasminogen Activator
PubMed: 35008762
DOI: 10.3390/ijms23010337 -
Molecules (Basel, Switzerland) Nov 2020Multivalent interactions frequently occur in biological systems and typically provide higher binding affinity and selectivity in target recognition than when only... (Review)
Review
Multivalent interactions frequently occur in biological systems and typically provide higher binding affinity and selectivity in target recognition than when only monovalent interactions are operative. Thus, taking inspiration by nature, bivalent or multivalent nucleic acid aptamers recognizing a specific biological target have been extensively studied in the last decades. Indeed, oligonucleotide-based aptamers are suitable building blocks for the development of highly efficient multivalent systems since they can be easily modified and assembled exploiting proper connecting linkers of different nature. Thus, substantial research efforts have been put in the construction of dimeric/multimeric versions of effective aptamers with various degrees of success in target binding affinity or therapeutic activity enhancement. The present review summarizes recent advances in the design and development of dimeric and multimeric DNA-based aptamers, including those forming G-quadruplex (G4) structures, recognizing different key proteins in relevant pathological processes. Most of the designed constructs have shown improved performance in terms of binding affinity or therapeutic activity as anti-inflammatory, antiviral, anticoagulant, and anticancer agents and their number is certainly bound to grow in the next future.
Topics: Anti-Inflammatory Agents; Anticoagulants; Antineoplastic Agents; Antiviral Agents; Aptamers, Nucleotide; CD3 Complex; Cell Adhesion Molecules; DNA; Dimerization; G-Quadruplexes; Humans; Immunoglobulin M; Phosphoproteins; Protein Structure, Secondary; Proto-Oncogene Proteins c-met; Pyrrolidines; RNA-Binding Proteins; Receptor Protein-Tyrosine Kinases; Receptors, Antigen, T-Cell; Vascular Endothelial Growth Factor A; Vitronectin; Nucleolin
PubMed: 33182593
DOI: 10.3390/molecules25225227