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Scientific Reports Jul 2024Durian (Durio zibethinus L.) fruit pulp is a rich source of γ-glutamylcysteine (γ-EC), a direct precursor to the antioxidant glutathione (GSH). This study elucidated...
Durian (Durio zibethinus L.) fruit pulp is a rich source of γ-glutamylcysteine (γ-EC), a direct precursor to the antioxidant glutathione (GSH). This study elucidated the in vitro neuroprotective potential of unripe durian fruit pulp extract (UDE) against HO-induced neurotoxicity in SH-SY5Y cells and neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Treatments with γ-EC, GSH standards, or UDE exhibited no cytotoxicity in SH-SY5Y and BV-2 cells, except at high concentrations. A 4-h pretreatment with 100 µM γ-EC or UDE containing 100 µM γ-EC significantly increased SH-SY5Y cell viability post HO induction. Moreover, a similar pretreatment reduced LPS-stimulated production of proinflammatory cytokines in BV-2 cells. The neuroprotective effect of UDE is primarily attributed to γ-EC provision and the promotion of GSH synthesis, which in turn elevates intracellular GSH levels and reduces proinflammatory cytokines. This study identifies γ-EC in UDE as a potential neuroprotective biomarker boosting intracellular GSH levels, providing insights into UDE's therapeutic potential.
Topics: Glutathione; Oxidative Stress; Plant Extracts; Neuroprotective Agents; Humans; Fruit; Animals; Inflammation; Lipopolysaccharides; Neuroprotection; Mice; Cell Survival; Hydrogen Peroxide; Antioxidants; Cell Line, Tumor; Cell Line; Cytokines; Dipeptides
PubMed: 38956206
DOI: 10.1038/s41598-024-65219-6 -
Scientific Reports Jul 2024The use of novel active ingredients for the functional modification of chitosan nanoformulations has attracted global attention. In this study, chitosan has been...
The use of novel active ingredients for the functional modification of chitosan nanoformulations has attracted global attention. In this study, chitosan has been functionalized via histidine to craft novel chitosan-histidine nanoformulation (C-H NF) using ionic gelation method. C-H NF exhibited elite physico-biochemical properties, influencing physiological and biochemical dynamics in Tomato. These elite properties include homogenous-sized nanoparticles (314.4 nm), lower PDI (0.218), viscosity (1.43 Cps), higher zeta potential (11.2 mV), nanoparticle concentration/ml (3.53 × 10), conductivity (0.046 mS/cm), encapsulation efficiency (53%), loading capacity (24%) and yield (32.17%). FTIR spectroscopy revealed histidine interaction with C-H NF, while SEM and TEM exposed its porous structure. Application of C-H NF to Tomato seedling and potted plants through seed treatment and foliar spray positively impacts growth parameters, antioxidant-defense enzyme activities, reactive oxygen species (ROS) content, and chlorophyll and nitrogen content. We claim that the histidine-functionalized chitosan nanoformulation enhances physico-biochemical properties, highlighting its potential to elevate biochemical and physiological processes of Tomato plant.
Topics: Solanum lycopersicum; Chitosan; Histidine; Nanoparticles; Reactive Oxygen Species; Antioxidants; Chlorophyll; Seedlings; Spectroscopy, Fourier Transform Infrared
PubMed: 38956171
DOI: 10.1038/s41598-024-64268-1 -
Scientific Reports Jul 2024We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with...
We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.
Topics: Excipients; Polysorbates; Vitamin E; Surface-Active Agents; Pyrrolidines; Molecular Dynamics Simulation; Thermodynamics; Hot Melt Extrusion Technology; Vinyl Compounds
PubMed: 38956156
DOI: 10.1038/s41598-024-65978-2 -
Scientific Reports Jul 2024Dysbindin-1, a protein encoded by the schizophrenia susceptibility gene DTNBP1, is reduced in the hippocampus of schizophrenia patients. It is expressed in various...
Dysbindin-1, a protein encoded by the schizophrenia susceptibility gene DTNBP1, is reduced in the hippocampus of schizophrenia patients. It is expressed in various cellular populations of the brain and implicated in dopaminergic and glutamatergic transmission. To investigate the impact of reduced dysbindin-1 in excitatory cells on hippocampal-associated behaviors and synaptic transmission, we developed a conditional knockout mouse model with deletion of dysbindin-1 gene in CaMKIIα expressing cells. We found that dysbindin-1 reduction in CaMKII expressing cells resulted in impaired spatial and social memories, and attenuation of the effects of glutamate N-methyl-d-asparate receptor (NMDAR) antagonist MK801 on locomotor activity and prepulse inhibition of startle (PPI). Dysbindin-1 deficiency in CaMKII expressing cells also resulted in reduced protein levels of NMDAR subunit GluN1 and GluN2B. These changes were associated with increased expression of immature dendritic spines in basiliar dendrites and abnormalities in excitatory synaptic transmission in the ventral hippocampus. These results highlight the functional relevance of dysbindin-1 in excitatory cells and its implication in schizophrenia-related pathologies.
Topics: Animals; Dysbindin; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Hippocampus; Mice; Mice, Knockout; Neurons; Schizophrenia; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Male; Dizocilpine Maleate; Behavior, Animal; Dendritic Spines; Nerve Tissue Proteins
PubMed: 38956130
DOI: 10.1038/s41598-024-65566-4 -
Scientific Reports Jul 2024This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of...
This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of dextranomer/hyaluronic acid copolymer in pediatric patients with vesicoureteral reflux. The data of patients without a previous history of surgery to treat vesicoureteral reflux and who underwent STING for the first time between September 2011 and November 2020 were investigated retrospectively. After considering exclusion criteria, of 199 patients, 127 patients and 180 renal units were suitable for inclusion. A renal unit-based evaluation was made. Age < 61 months (univariate: p = 0.001, multivariate: p = 0.015, HR: 2.352 (1.181-4.686), OR (95% CI)), moderate reflux level (grade 3) (univariate: p < 0.001, multivariate: p = 0.019, HR: 2.703 (1.177-6.209), OR (95% CI)), DRF (differential renal function) < 45 (univariate: p = 0.020, multivariate: p = 0.047, HR: 1.992 (1.009-3.935), OR (95% CI)), and UDR (ureteral diameter ratio) > 0.15 (univariate: p < 0.001, multivariate: p = 0.005, HR: 2.786 (1.368-5.672), OR (95% CI)) were found predictors of reflux persistence after STING surgery both univariate and multivariate analysis. High reflux level (grade 4-5) was statistically significant in univariate analysis (p < 0.001) but not statistically significant in multivariate analysis (p = 0.215). In our study, UDR and DRF were found to be factors affecting reflux persistence. UDR and DRF should be considered in order to predict reflux resolution in patients who will undergo STING.
Topics: Humans; Vesico-Ureteral Reflux; Hyaluronic Acid; Dextrans; Female; Male; Child, Preschool; Retrospective Studies; Infant; Child; Injections; Treatment Outcome
PubMed: 38956126
DOI: 10.1038/s41598-024-62449-6 -
Nature Communications Jul 2024Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot...
Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5-3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.
Topics: Humans; Sodium-Coupled Vitamin C Transporters; Ascorbic Acid; Cryoelectron Microscopy; Biological Transport; Sodium; Models, Molecular; Protein Multimerization; Protein Binding; HEK293 Cells; Protein Conformation
PubMed: 38956111
DOI: 10.1038/s41467-024-49899-2 -
Scientific Reports Jul 2024Soil salinity is a major nutritional challenge with poor agriculture production characterized by high sodium (Na) ions in the soil. Zinc oxide nanoparticles (ZnO NPs)...
Salt stress amelioration and nutrient strengthening in spinach (Spinacia oleracea L.) via biochar amendment and zinc fortification: seed priming versus foliar application.
Soil salinity is a major nutritional challenge with poor agriculture production characterized by high sodium (Na) ions in the soil. Zinc oxide nanoparticles (ZnO NPs) and biochar have received attention as a sustainable strategy to reduce biotic and abiotic stress. However, there is a lack of information regarding the incorporation of ZnO NPs with biochar to ameliorate the salinity stress (0, 50,100 mM). Therefore, the current study aimed to investigate the potentials of ZnO NPs application (priming and foliar) alone and with a combination of biochar on the growth and nutrient availability of spinach plants under salinity stress. Results demonstrated that salinity stress at a higher rate (100 mM) showed maximum growth retardation by inducing oxidative stress, resulted in reduced photosynthetic rate and nutrient availability. ZnO NPs (priming and foliar) alone enhanced growth, chlorophyll contents and gas exchange parameters by improving the antioxidant enzymes activity of spinach under salinity stress. While, a significant and more pronounced effect was observed at combined treatments of ZnO NPs with biochar amendment. More importantly, ZnO NPs foliar application with biochar significantly reduced the Na contents in root 57.69%, and leaves 61.27% of spinach as compared to the respective control. Furthermore, higher nutrient contents were also found at the combined treatment of ZnO NPs foliar application with biochar. Overall, ZnO NPs combined application with biochar proved to be an efficient and sustainable strategy to alleviate salinity stress and improve crop nutritional quality under salinity stress. We inferred that ZnO NPs foliar application with a combination of biochar is more effectual in improving crop nutritional status and salinity mitigation than priming treatments with a combination of biochar.
Topics: Spinacia oleracea; Charcoal; Salt Stress; Zinc Oxide; Plant Leaves; Photosynthesis; Zinc; Nutrients; Chlorophyll; Seeds; Antioxidants; Soil; Oxidative Stress; Salinity
PubMed: 38956110
DOI: 10.1038/s41598-024-65834-3 -
Nature Communications Jul 2024Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially...
Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.
Topics: Dopamine; Animals; Humans; Optogenetics; Mice; Male; Corpus Striatum; Receptors, Dopamine; Mice, Inbred C57BL; Allosteric Regulation; Photometry; HEK293 Cells
PubMed: 38956067
DOI: 10.1038/s41467-024-49442-3 -
Mikrochimica Acta Jul 2024Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment...
A double boronic acid affinity "sandwich" SERS biosensor based on magnetic boronic acid controllable-oriented imprinting for high-affinity biomimetic specific recognition and rapid detection of target glycoproteins.
Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.
Topics: Boronic Acids; Biosensing Techniques; Gold; Humans; Spectrum Analysis, Raman; Silver; Metal Nanoparticles; Limit of Detection; Transferrin; Molecular Imprinting; Molecularly Imprinted Polymers; Glycoproteins; Biomimetic Materials; Dopamine; Sulfhydryl Compounds
PubMed: 38955823
DOI: 10.1007/s00604-024-06522-x -
East Asian Archives of Psychiatry :... Jun 2024We conducted a systematic review evaluating the efficacy of rivastigmine augmentation for treatment-refractory posttraumatic stress disorder (PTSD). The Preferred... (Review)
Review
We conducted a systematic review evaluating the efficacy of rivastigmine augmentation for treatment-refractory posttraumatic stress disorder (PTSD). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The databases Ovid MEDLINE, PubMed, CINAHL, and EMBASE were searched using key words: 'rivastigmine' OR 'Exelon' OR 'rivastigmine augmentation' OR 'Exelon augmentation' AND 'posttraumatic stress disorder*' OR 'post-traumatic stress disorder*' OR 'PTSD' OR 'combat disorder*' OR 'post-traumatic symptoms'. The asterisk specified plural forms of the relevant word. Four papers were identified, comprising one double-blind randomised controlled trial, one non-controlled open trial, one case series (presenting three case studies), and one paper with two case studies. The randomised controlled trial found no statistically significant difference in efficacy, using the PTSD CheckList-Military Version as the relevant outcomes measure, between the active add-on rivastigmine interventions and placebo or treatment as usual. The open trial, although reporting relatively positive outcomes, had a weak study design and lacked reporting of key information, including participant sex and age and pre-rivastigmine PTSD measures. The assessment of efficacy was based on participants' reporting of subjective benefits, and clinician-rating using a Clinical Global Impression, rather than established PTSD assessments scales. Although the five case studies reported improvement in PTSD symptoms, there were confounding factors and limitations in clinical and demographic data, warranting caution regarding attributed benefits. There is a lack of methodologically robust evidence supporting the efficacy of add-on rivastigmine for the treatment of refractory PTSD. Additional research may help in further evaluating its possible clinical efficacy.
Topics: Rivastigmine; Humans; Stress Disorders, Post-Traumatic; Neuroprotective Agents; Cholinesterase Inhibitors
PubMed: 38955788
DOI: 10.12809/eaap2353