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Brain Research Jun 2024Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood...
Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood disorders like depression. The balance between the generation of reactive oxygen species (ROS) and the cell's antioxidant defenses, when disrupted, can lead to neuronal damage and neurologic dysfunction. In this study, we focused on the pathogenic role of oxidative stress in various neurologic disease models in vitro and investigated the neuroprotective capabilities of some novel bicyclic γ-butyrolactone compounds, with particular emphasis on the compound designated as 'bd'. Our investigation leveraged the HT22 and SH-SY5Y cells to model oxidative stress induced by HO or corticosterone (CORT), common triggers of neuronal damage in neurodegenerative and mood disorders. We discovered that compound bd robustly reduced ROS production and suppressed neuronal apoptosis, suggesting its potential in treating a wider array of neurological conditions influenced by oxidative stress. In conclusion, our research underscores the importance of addressing oxidative stress in the context of diverse neurological disorders. The identification of compound bd as a neuroprotective agent with potential efficacy against ROS-induced apoptosis in neural cells opens new horizons for therapeutic development, offering hope for patients suffering from neurodegenerative diseases, depression, and other stress-related neurological conditions.
PubMed: 38942352
DOI: 10.1016/j.brainres.2024.149099 -
Neurobiology of Disease Jun 2024Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can...
Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can be responsible for many major medical complications, moreover, in addition to the various systemic impairments, patients with AN undergo morphological and physiological changes affecting the cerebral cortex. Through immunohistochemical studies on portions of postmortem human brain of people affected by AN and healthy individuals, and western blot studies on leucocytes of young patients and healthy controls, this study investigated the role in the afore-mentioned processes of altered redox state. The results showed that the brain volume reduction in AN could be due to an increase in the rate of cell death, mainly by apoptosis, in which mitochondria, main cellular organelles affected by a decreased dietary intake, and a highly compromised intracellular redox balance, may play a pivotal role.
PubMed: 38942323
DOI: 10.1016/j.nbd.2024.106580 -
The Science of the Total Environment Jun 2024Standardisation and validation of methods for microplastics research is essential. A major methodological challenge is the removal of planktonic organisms from marine...
Standardisation and validation of methods for microplastics research is essential. A major methodological challenge is the removal of planktonic organisms from marine water samples allowing for the identification of microplastics associated to planktonic communities. To improve the reproducibility and accuracy of digestion methods for the removal of planktonic biomass, we compared and modified existing chemical digestion methods. These digestion methods included an acidic digestion using nitric acid, alkaline digestions with potassium hydroxide (alkaline 1 digestion) and sodium hydroxide from drain cleaner (alkaline 2 digestion), an oxidative digestion using sodium dodecyl sulfate with hydrogen peroxide, and an enzymatic digestion using enzyme drain clean pellets. Chemical digestion of three densities of zooplankton communities (high, medium, and low) in the presence of five commonly found environmental microplastic pollutants (polyamide, polyethylene, polyethylene terephthalate, polypropylene, and polystyrene) were performed for each treatment. The chemical treatments were assessed for (i) their digestion efficiency of zooplankton communities by different biomass densities, and (ii) their impact on microplastic particles through the comparison of both chemical (Raman spectroscopy) and physical (length, width, and visual) changes, between the pre-treatment and post-treatment microplastic particles. The alkaline 1, alkaline 2 and oxidative methods demonstrated significantly better digestion efficiency (p < 0.05) than the modified enzymatic and acidic treatments. The acidic, alkaline 1, and alkaline 2, treatments caused the most damages to the microplastic particles. We suggest future studies to implement the oxidative digestion method with sodium dodecyl sulfate and hydrogen peroxide because of its high digestion efficiency, and low damage to microplastic particles. This method is similar to the wet peroxide oxidation digestion method used throughout the literature but can be implemented at a lower cost.
PubMed: 38942303
DOI: 10.1016/j.scitotenv.2024.174279 -
Journal of Lipid Research Jun 2024The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on...
The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on extra-coronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extra-coronary vascular disease and incident major adverse limb events (MALE). 446 participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extra-coronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (OR 2.14 95% CI: 1.03, 4.44) and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extra-coronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extra-coronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries. These results lay a foundation in support of studying Lp(a) lowering medications and their effect on limb-related complications.
PubMed: 38942114
DOI: 10.1016/j.jlr.2024.100585 -
European Journal of Dentistry Jun 2024The proper closure of the access cavity between appointments during endodontic treatment is paramount and relies on temporary fillings. This systematic review evaluates...
The proper closure of the access cavity between appointments during endodontic treatment is paramount and relies on temporary fillings. This systematic review evaluates the effectiveness of zinc oxide-based materials and glass-ionomer cement (GIC) as temporary coronal sealers after root canal treatment in extracted human teeth. Three databases were searched to identify randomized clinical trials that examined the sealing properties of various temporary sealing materials using dyes or stains as indicators. A total of seven studies that fulfilled the eligibility criteria were critically analyzed. These indicated significant variations in the relative sealing ability of the coronal breach of endodontically treated teeth, either by zinc oxide or GIC-based materials. While GIC-based material (e.g., Fuji IX and Fuji II) exhibited superior sealing of single-rooted teeth, zinc oxide-based material (e.g., Cavit, Coltosol, Caviton) also showed promising attributes. Resin-modified GIC formulations displayed enhanced physical properties, yet challenges related to adhesive failure and shrinkage during polymerization were observed. Zinc oxide-based materials have demonstrated superior coronal sealing effectiveness over certain GIC in controlled settings. Their premixed nature ensures consistent application and hygroscopic properties improve cavity sealing. However, the focus on dye penetration tests for microleakage may not fully represent the risk of bacterial infiltration. Thus, studies are crucial for validating these findings in clinical contexts.
PubMed: 38942056
DOI: 10.1055/s-0044-1782695 -
European Journal of Dentistry Jun 2024Sintering influences the optical properties of zirconia. This study examined the effect of altering sintering temperature and time of monochrome (Mo) and multilayer...
OBJECTIVES
Sintering influences the optical properties of zirconia. This study examined the effect of altering sintering temperature and time of monochrome (Mo) and multilayer (Mu) 5 mol% yttria-partially stabilized zirconia (5Y-PSZ) on color characteristics.
MATERIALS AND METHODS
Three hundred specimens (width × length × thickness = 10 × 20 × 2 mm) were prepared from Mo and Mu (with cervical [C], middle [M], and incisal [I] region) 5Y-PSZ and randomly sintered at decreasing (Td: 1,450°C), regular (Tr: 1,500°C), and increasing (TI: 1,550°C) sintering temperature, with extremely short (He: 10 minutes), ultrashort (Hu: 15 minutes), short (Hs: 30 minutes), and regular (Hr: 135 minutes) sintering time ( = 15/group). Color appearance ( ), translucency parameter (TP), contrast ratio (CR), opalescence parameter (OP), and color appearance difference (∆ ) were evaluated in the CIE L*a*b* system. Microstructures were evaluated by scanning electron microscope (SEM) and X-ray diffractometer (XRD).
STATISTICAL ANALYSIS
Analysis of variance (ANOVA) and Bonferroni comparisons were determined for significant differences ( < 0.05).
RESULTS
Significant differences in color parameters upon zirconia type, sintering temperature, and sintering time, and their interactions were indicated ( < 0.05). Increasing sintering temperature and extended sintered time resulted in larger grain, reduced tetragonal-to-monoclinic phase transformation, and significantly increased the TP and OP, but decreased the CR and ∆ ( < 0.05). Decreasing sintering temperature and time led to clinically unacceptable color appearance.
CONCLUSION
Mo was found to be more translucent than Mu. To achieve the most favorable optical properties, increasing sintering temperature and extending sintering time are recommended. Decreasing sintering temperature is not suggested. However, shortened sintering time is feasible, but it needs sintering with increasing sintering temperature to achieve a promising color appearance.
PubMed: 38942053
DOI: 10.1055/s-0044-1787700 -
Biomedicine & Pharmacotherapy =... Jun 2024Alzheimer's disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist...
Ameliorative effect of vanillic acid against scopolamine-induced learning and memory impairment in rat via attenuation of oxidative stress and dysfunctional synaptic plasticity.
Alzheimer's disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA's neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles' density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study's findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.
PubMed: 38941895
DOI: 10.1016/j.biopha.2024.117000 -
Biomedicine & Pharmacotherapy =... Jun 2024In cell-based bone augmentation, transplanted cell dysfunction and apoptosis can occur due to oxidative stress caused by the overproduction of reactive oxygen species...
In cell-based bone augmentation, transplanted cell dysfunction and apoptosis can occur due to oxidative stress caused by the overproduction of reactive oxygen species (ROS). Edaravone (EDA) is a potent free radical scavenger with potential medical applications. This study aimed to investigate the effect of controlling oxidative stress on bone regeneration using EDA. Bone marrow-derived cells were collected from 4-week-old rats, and EDA effects on cell viability and osteogenic differentiation were evaluated. Collagen gels containing PKH26-prelabeled cells were implanted into the calvarial defects of 12-week-old rats, followed by daily subcutaneous injections of normal saline or 500 μM EDA for 4 d. Bone formation was examined using micro-computed tomography and histological staining. Immunofluorescence staining was performed for markers of oxidative stress, macrophages, osteogenesis, and angiogenesis. EDA suppressed ROS production and hydrogen peroxide-induced apoptosis, recovering cell viability and osteoblast differentiation. EDA treatment in vivo increased new bone formation. EDA induced the transition of the macrophage population toward the M2 phenotype. The EDA group also exhibited stronger immunofluorescence for vascular endothelial growth factor and CD31. In addition, more PKH26-positive and PKH26-osteocalcin-double-positive cells were observed in the EDA group, indicating that transplanted cell survival was prolonged, and they differentiated into bone-forming cells. This could be attributed to oxidative stress suppression at the transplantation site by EDA. Collectively, local administration using EDA facilitates bone regeneration by improving the local environment and angiogenesis, prolonging survival, and enhancing the osteogenic capabilities of transplanted cells.
PubMed: 38941894
DOI: 10.1016/j.biopha.2024.117032 -
Molecular Genetics and Metabolism Jun 2024Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary...
Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary across the lifespan and onset may occur at any time from the early neonatal period to advanced adulthood. Historically, some patients, in particular those with late onset disease, have experienced significant benefit from riboflavin supplementation. GAII has been considered an autosomal recessive condition caused by pathogenic variants in the gene encoding electron-transfer flavoprotein ubiquinone-oxidoreductase (ETFDH) or in the genes encoding electron-transfer flavoprotein subunits A and B (ETFA and ETFB respectively). Variants in genes involved in riboflavin metabolism have also been reported. However, in some patients, molecular analysis has failed to reveal diagnostic molecular results. In this study, we report the outcome of molecular analysis in 28 Australian patients across the lifespan, 10 paediatric and 18 adult, who had a diagnosis of glutaric aciduria type II based on both clinical and biochemical parameters. Whole genome sequencing was performed on 26 of the patients and two neonatal onset patients had targeted sequencing of candidate genes. The two patients who had targeted sequencing had biallelic pathogenic variants (in ETFA and ETFDH). None of the 26 patients whose whole genome was sequenced had biallelic variants in any of the primary candidate genes. Interestingly, nine of these patients (34.6%) had a monoallelic pathogenic or likely pathogenic variant in a single primary candidate gene and one patient (3.9%) had a monoallelic pathogenic or likely pathogenic variant in two separate genes within the same pathway. The frequencies of the damaging variants within ETFDH and FAD transporter gene SLC25A32 were significantly higher than expected when compared to the corresponding allele frequencies in the general population. The remaining 16 patients (61.5%) had no pathogenic or likely pathogenic variants in the candidate genes. Ten (56%) of the 18 adult patients were taking the selective serotonin reuptake inhibitor antidepressant sertraline, which has been shown to produce a GAII phenotype, and another two adults (11%) were taking a serotonin-norepinephrine reuptake inhibitor antidepressant, venlafaxine or duloxetine, which have a mechanism of action overlapping that of sertraline. Riboflavin deficiency can also mimic both the clinical and biochemical phenotype of GAII. Several patients on these antidepressants showed an initial response to riboflavin but then that response waned. These results suggest that the GAII phenotype can result from a complex interaction between monoallelic variants and the cellular environment. Whole genome or targeted gene panel analysis may not provide a clear molecular diagnosis.
PubMed: 38941880
DOI: 10.1016/j.ymgme.2024.108516 -
Comparative Biochemistry and... Jun 2024Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its...
Comparative physiological, biochemical and transcriptomic analyses to reveal potential regulatory mechanisms in response to starvation stress in Cipangopaludina chinensis.
Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its limited prey options. However, the underlying response mechanisms to combat starvation have not been investigated in depth. We collected C. chinensis under several times of starvation stress (0, 7, 30, and 60 days) for nutrient, biochemical characteristics and transcriptome analyses. The results showed that prolonged starvation stress (> 30 days) caused obvious fluctuations in the nutrient composition of snails, with dramatic reductions in body weight, survival and digestive enzyme activity (amylase, protease, and lipase), and markedly enhanced the antioxidant enzyme activities of the snails. Comparative transcriptome analyses revealed 3538 differentially expressed genes (DEGs), which were significantly associated with specific starvation stress-responsive pathways, including oxidative phosphorylation and alanine, aspartate, and glutamate metabolism. Then, we identified 40 candidate genes (e.g., HACD2, Cp1, CYP1A2, and GPX1) response to starvation stress through STEM and WGCNA analyses. RT-qPCR verified the accuracy and reliability of the high-throughput sequencing results. This study provides insights into snail overwintering survival and the potential regulatory mechanisms of snail adaptation to starvation stress.
PubMed: 38941864
DOI: 10.1016/j.cbd.2024.101279