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RSC Advances Jun 2024Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger...
Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including , , and have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.
PubMed: 38952927
DOI: 10.1039/d4ra00796d -
Clinical Interventions in Aging 2024To investigate association between optic disc parameters analyzed by optical coherence tomography (OCT) and occurrence of peripheral retinal tears in patients with...
BACKGROUND
To investigate association between optic disc parameters analyzed by optical coherence tomography (OCT) and occurrence of peripheral retinal tears in patients with symptomatic posterior vitreous detachment (PVD).
METHODS
This cross-sectional study enrolled 75 patients with symptoms of acute PVD, who were allocated into two groups based on whether a peripheral retinal tear occurred or not.
RESULTS
When comparing the average retinal nerve fiber layer (RNFL) thickness (μm) between retinal tear and control groups, it was shown that patients with a retinal tear have a significantly higher (87.18 [95% confidence interval (CI), 84.47 to 89.9] vs 81.14 [95% CI, 77.81 to 84.46], = 0.005) average RNFL thickness. Furthermore, we observed a significant difference (0.13, 0.06 to 0.22 vs 0.07, 0.04 to 0.1, = 0.036, Mann-Whitney -test) in the size of cup volume (mm) between the tear and control groups, respectively. Linear regression showed a significant decrease ( = 0.029) in average RNFL thickness with increasing age, but without a significant difference between the two groups. There was no statistically significant difference between the tear and control groups in terms of rim area, disc area, and average cup-to-disc ratio.
CONCLUSION
Patients with a higher average RNFL thickness and larger cup volume measured by OCT were more prone to develop a peripheral retinal tear. Increased peripapillary average RNFL thickness due to trauma and subsequent inflammation, possibly related to the more adherent posterior hyaloid membrane to the retina, may also indicate strengthened adhesions in the areas of the peripheral retina where retinal tears occur. OCT analysis of the optic nerve head may be used in everyday clinical practice as a predictor of the development of peripheral retinal tears in patients with symptomatic PVD.
Topics: Humans; Cross-Sectional Studies; Male; Tomography, Optical Coherence; Female; Vitreous Detachment; Middle Aged; Optic Disk; Retinal Perforations; Aged; Nerve Fibers; Adult; Linear Models
PubMed: 38952872
DOI: 10.2147/CIA.S466511 -
BioRxiv : the Preprint Server For... Jun 2024This study illustrates a vital role for ankyrin-B in lens architecture, growth and function through its involvement in membrane protein and spectrin-actin cytoskeletal...
This study illustrates a vital role for ankyrin-B in lens architecture, growth and function through its involvement in membrane protein and spectrin-actin cytoskeletal organization and stability The transparent ocular lens is essential for vision by focusing light onto the retina. Despite recognizing the importance of its unique cellular architecture and mechanical properties, the molecular mechanisms governing these attributes remain elusive. This study aims to elucidate the role of ankyrin-B (AnkB), a membrane scaffolding protein, in lens cytoarchitecture, growth and function using a conditional knockout (cKO) mouse model. AnkB cKO mouse has no defects in lens morphogenesis, but exhibited changes that supported a global role for AnkB in maintenance of lens clarity, size, cytoarchitecture, and stiffness. Notably, absence of AnkB led to nuclear cataract formation, evident from P16. AnkB cKO lens fibers exhibit progressive disruption in membrane organization of the spectrin-actin cytoskeleton, channel proteins, cell-cell adhesion, shape change, loss and degradation of several membrane proteins (e.g., NrCAM. N-cadherin and aquaporin-0) along with a disorganized plasma membrane and impaired ball-and-socket membrane interdigitations. Furthermore, absence of AnkB led to decreased lens stiffness. Collectively, these results illustrate the essential role for AnkB in lens architecture, growth and function through its involvement in membrane protein and cytoskeletal organization.
PubMed: 38952798
DOI: 10.1101/2024.06.12.598702 -
Clinical Epidemiology 2024Frozen shoulder may be an early preclinical symptom of Parkinson's disease (PD).
BACKGROUND
Frozen shoulder may be an early preclinical symptom of Parkinson's disease (PD).
OBJECTIVE
To examine PD risk after frozen shoulder diagnosis and to evaluate this disorder as a possible manifestation of parkinsonism preceding the clinical recognition of PD and possible target for screening.
METHODS
Danish population-based medical registries were used to identify patients aged ≥40 years with a first-time frozen shoulder diagnosis (1995-2016). A comparison cohort was randomly selected from the general population matched on age and sex. To address detection bias and the specificity of frozen shoulder diagnosis, we performed a sensitivity analysis, using similar matching criteria to select a cohort of patients with back pain diagnosis. The outcome was incident PD. Cumulative incidences and adjusted hazard ratios (HRs) were estimated with 95% confidence intervals (CIs).
RESULTS
We identified 37,041 individuals with frozen shoulder, 370,410 general population comparators, and 111,101 back pain comparators. The cumulative incidence of PD at 0-22 years follow-up was 1.51% in the frozen shoulder cohort, 1.03% in the general population cohort, and 1.32% in the back pain cohort. For frozen shoulder versus general population, adjusted HRs were 1.94 (CI: 1.20-3.13) at 0-1 years and 1.45 (CI: 1.24-1.70) at 0-22 years follow-up. For frozen shoulder versus back pain, adjusted HRs were 0.89 (CI: 0.54-1.46) and 1.01 (CI: 0.84-1.21), respectively.
CONCLUSION
Patients with frozen shoulder had an increased PD risk compared with the general population, although the absolute risks were low. Frozen shoulder might sometimes represent early manifestations of PD. Detection bias probably cannot account for the increased PD risk during the long-term follow-up.
PubMed: 38952571
DOI: 10.2147/CLEP.S463571 -
Journal of Inflammation Research 2024Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for...
PURPOSE
Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present.
METHODS
We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways.
RESULTS
PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, β-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, β-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, β-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1.
CONCLUSION
The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP.
PubMed: 38952564
DOI: 10.2147/JIR.S459449 -
Cancer Management and Research 2024Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like...
BACKGROUND
Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may be associated with cardioprotective properties.
PURPOSE
This study aims to determine the protective effects of different semaglutide (SEM) doses on DOX-induced cardiotoxicity in a rat model.
METHODOLOGY
Thirty-five female Wistar rats were divided into five groups. The first group received distilled water as a negative control (NC); the positive control (PC) group received distilled water plus DOX; the third group (SL) received a low dose of SEM (0.06 mg/kg) plus DOX; the fourth group (SM) received a moderate dose of SEM (0.12 mg/kg) plus DOX; and the fifth group (SH) received a high dose of SEM (0.24 mg/kg) plus DOX. Blood samples were collected on day 8 to assess serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, and vascular cell adhesion molecule 1 (VCAM-1). Cardiac tissue was sent for histopathological analysis.
RESULTS
DOX increased the total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), LDH, and CKP levels. Moderate and high doses of semaglutide significantly reduced serum cholesterol levels (* = 0.0199), (** = 0.0077), respectively. A significant reduction (*** = 0.0013) in total body weight after treatment with SEM was observed in the SL group and a highly significant reduction (**** < 0.0001) was observed in the SM and SH groups. SEM at all doses reduced CPK levels. The SL group showed a significant reduction in troponin level (*=0.0344). Serum LDH levels were reduced by all three SEM doses. The histopathological findings support the biochemical results.
CONCLUSION
Semaglutide may possess cardioprotective properties against DOX-induced cardiotoxicity in a rat model by decreasing serum biochemical markers of cardiotoxicity.
PubMed: 38952352
DOI: 10.2147/CMAR.S468453 -
Clinical Epigenetics Jun 2024Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores...
BACKGROUND
Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins.
RESULTS
In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value < 8.3 × 10). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5, and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjusted p-value < 8.3 × 10). In a preterm subgroup (n = 217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis.
CONCLUSIONS
Low birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.
Topics: Humans; Saliva; Female; Infant, Newborn; Gestational Age; Epigenesis, Genetic; Male; DNA Methylation; Premature Birth; Pregnancy; Infant, Premature; Social Class; Adult; Inflammation
PubMed: 38951914
DOI: 10.1186/s13148-024-01701-2 -
Alzheimer's Research & Therapy Jun 2024The Amyloid precursor protein (APP) is a transmembrane glycoprotein from which amyloid-β (Aβ) peptides are generated after proteolytic cleavage. Aβ peptides are the... (Review)
Review
The Amyloid precursor protein (APP) is a transmembrane glycoprotein from which amyloid-β (Aβ) peptides are generated after proteolytic cleavage. Aβ peptides are the main constituent of amyloid plaques in Alzheimer's Disease (AD). The physiological functions of APP in the human adult brain are very diverse including intracellular signaling, synaptic and neuronal plasticity, and cell adhesion, among others. There is growing evidence that APP becomes dysfunctional in AD and that this dyshomeostasis may impact several APP functions beyond Aβ generation. The vast majority of current anti-amyloid approaches in AD have focused on reducing the synthesis of Aβ or increasing the clearance of brain Aβ aggregates following a paradigm in which Aβ plays a solo in APP dyshomeostasis. A wider view places APP at the center stage in which Aβ is an important, but not the only, factor involved in APP dyshomeostasis. Under this paradigm, APP dysfunction is universal in AD, but with some differences across different subtypes. Little is known about how to approach APP dysfunction therapeutically beyond anti-Aβ strategies. In this review, we will describe the role of APP dyshomeostasis in AD beyond Aβ and the potential therapeutic strategies targeting APP.
Topics: Humans; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Amyloid beta-Peptides; Brain
PubMed: 38951839
DOI: 10.1186/s13195-024-01504-w -
BMC Genomics Jun 2024Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune...
BACKGROUND
Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune response against a wide array of viruses. In mammals, Viperin exerts its antiviral function through enzymatic conversion of cytidine triphosphate (CTP) into its antiviral analog ddhCTP as well as through interactions with host proteins involved in innate immune signaling and in metabolic pathways exploited by viruses during their life cycle. However, how Viperin modulates the antiviral response in fish remains largely unknown.
RESULTS
For this purpose, we developed a fathead minnow (Pimephales promelas) clonal cell line in which the unique viperin gene has been knocked out by CRISPR/Cas9 genome-editing. In order to decipher the contribution of fish Viperin to the antiviral response and its regulatory role beyond the scope of the innate immune response, we performed a comparative RNA-seq analysis of viperin and wildtype cell lines upon stimulation with recombinant fathead minnow type I interferon.
CONCLUSIONS
Our results revealed that Viperin does not exert positive feedback on the canonical type I IFN but acts as a negative regulator of the inflammatory response by downregulating specific pro-inflammatory genes and upregulating repressors of the NF-κB pathway. It also appeared to play a role in regulating metabolic processes, including one carbon metabolism, bone formation, extracellular matrix organization and cell adhesion.
Topics: Animals; Cyprinidae; Inflammation; Immunity, Innate; Fish Proteins; Cell Line; CRISPR-Cas Systems; Interferon Type I; Gene Editing; Gene Expression Regulation
PubMed: 38951796
DOI: 10.1186/s12864-024-10566-x -
BMC Oral Health Jun 2024Gutta-percha (GP) combined with an endodontic sealer is still the core material most widely used for tridimensional obturation. The sealer acts as a bonding agent...
BACKGROUND
Gutta-percha (GP) combined with an endodontic sealer is still the core material most widely used for tridimensional obturation. The sealer acts as a bonding agent between the GP and the root dentinal walls. However, one of the main drawbacks of GP core material is the lack of adhesiveness to the sealer. ZnO thin films have many remarkable features due to their considerable bond strength, good optical quality, and excellent piezoelectric, antibacterial, and antifungal properties, offering many potential applications in various fields. This study aimed to explore the influence of GP surface's functionalization with a nanostructured ZnO thin film on its adhesiveness to endodontic sealers.
METHODS
Conventional GP samples were divided randomly into three groups: (a) Untreated GP (control); (b) GP treated with argon plasma (PT); (c) Functionalized GP (PT followed by ZnO thin film deposition). GP's surface functionalization encompassed a multi-step process. First, a low-pressure argon PT was applied to modify the GP surface, followed by a ZnO thin film deposition via magnetron sputtering. The surface morphology was assessed using SEM and water contact angle analysis. Further comprehensive testing included tensile bond strength assessment evaluating Endoresin and AH Plus Bioceramic sealers' adhesion to GP. ANOVA procedures were used for data statistical analysis.
RESULTS
The ZnO thin film reproduced the underlying surface topography produced by PT. ZnO thin film deposition decreased the water contact angle compared to the control (p < 0.001). Endoresin showed a statistically higher mean bond strength value than AH Plus Bioceramic (p < 0.001). There was a statistically significant difference between the control and the ZnO-functionalized GP (p = 0.006), with the latter presenting the highest mean bond strength value.
CONCLUSIONS
The deposition of a nanostructured ZnO thin film on GP surface induced a shift towards hydrophilicity and an increased GP's adhesion to Endoresin and AH Bioceramic sealers.
Topics: Zinc Oxide; Root Canal Filling Materials; Nanostructures; Gutta-Percha; Dental Bonding; Surface Properties; Humans; Materials Testing; Adhesiveness; Microscopy, Electron, Scanning; Tensile Strength
PubMed: 38951790
DOI: 10.1186/s12903-024-04496-z