ABSTRACT
Butterfly wings possess distinct micro/nanostructures that contribute to their vibrant coloration, light-trapping capabilities, and sensitivity to various stimuli. These complex features have inspired the creation of diverse devices and systems, such as sensors, photovoltaics, photocatalysis, and robotics. Specifically, the wing scales of the Emerald Swallowtail (Papilio palinurus) display iridescent, polarization-sensitive, and retroreflective colors due to their hierarchical structures. However, current technologies fail to mimic these natural designs fully, limiting their practical application in everyday life. In this study, we introduce a groundbreaking method for fabricating artificial wing scales that emulate the biological structure's functionality with a much simpler geometry. By integrating self-graded lossy media into metallic micro-concavity arrays, we achieve pronounced iridescent effects in both coaxial and non-coaxial arrangements, while preserving retroreflective properties. In particular, the simplified design allows for switchable color patterns based on the viewing angle. Demonstrating the concept, we successfully employ these conspicuous retroreflectors in hydrogen gas detection and the bi-directional/switchable recognition of patterned signals.
Subject(s)
Biosensing Techniques , Butterflies , Wings, Animal , Biosensing Techniques/instrumentation , Animals , Equipment Design , Hydrogen/chemistry , Hydrogen/analysis , Color , Nanostructures/chemistryABSTRACT
BACKGROUND: Mangosteens, a naturally occurring xanthones, found abundantly in mangosteen fruits. The anti-skin aging potential of γ-mangosteen (GM) remains unexplored; therefore, we investigated the UVB-induced anti-skin aging of GM via activation of autophagy. HYPOTHESIS: We hypothesized that GM exerts antioxidant and anti-aging capabilities both in vitro and in vivo through activation of autophagy as well as control of KEAP1/NRF2 signaling and MAPKs/AP-1/NF-κB-mediated MMPs pathways. METHODS: The anti-skin aging effects of GM were studied using HDF cells and a mice model. Various assays, such as DPPH, ABTS, CUPRAC, FRAP, and ROS generation, assessed antioxidant activities. Kits measured antioxidant enzymes, SA-ß-gal staining, collagen, MDA content, si-RNA experiments, and promoter assays. Western blotting evaluated protein levels of c-Jun, c-Fos, p-IκBα/ß, p-NF-κB, MAPK, MMPs, collagenase, elastin, KEAP1, NRF2, HO-1, and autophagy-related proteins. RESULTS: GM exhibited strong antioxidant, collagenase and elastase enzyme inhibition activity surpassing α- and ß-mangosteen. GM competitively inhibited elastase with a Ki value of 29.04 µM. GM orchestrated the KEAP1-NRF2 pathway, enhancing HO-1 expression, and suppressed UVB-induced ROS in HDF cells. NRF2 knockdown compromised GM's antioxidant efficacy, leading to uncontrolled ROS post-UVB. GM bolstered endogenous antioxidants, curbing lipid peroxidation in UVB-exposed HDF cells and BALB/c mice. GM effectively halted UVB-induced cell senescence, and reduced MMP-1/-9, while elevated TIMP-1 levels, augmented COL1A1, ELN, and HAS-2 expression in vitro and in vivo. Additionally, it suppressed UVB-induced MAPKs, AP-1, NF-κB phosphorylation. Pharmacological inhibitors synergistically enhanced GM's anti-skin aging potential. Moreover, GM inhibited UVB-induced mTOR activation, upregulated LC3-II, Atg5, Beclin 1, and reduced p62 in both UVB induced HDF cells and BALB/c mice, while blocking of autophagy successfully halt the GM effects against the UVB-induced increase of cell senescence, degradation of collagen through upregulation of MMP-1, underscoring GM's substantial anti-skin aging impact via autophagy induction in vitro and in vivo. CONCLUSION: Together, GM has potent antioxidant and anti-skin aging ingredients that can be used to formulate skin care products for both the nutraceutical and cosmeceutical industries.
Subject(s)
Antioxidants , Autophagy , Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , NF-kappa B , Signal Transduction , Skin Aging , Transcription Factor AP-1 , Animals , Skin Aging/drug effects , Skin Aging/radiation effects , Autophagy/drug effects , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-kappa B/metabolism , Transcription Factor AP-1/metabolism , Antioxidants/pharmacology , Mice , Signal Transduction/drug effects , Matrix Metalloproteinases/metabolism , Humans , Ultraviolet Rays/adverse effects , Down-Regulation/drug effects , Fibroblasts/drug effects , Fibroblasts/radiation effectsABSTRACT
The structure and process of the graphene/Si heterojunction near-infrared photodetector were optimized to enhance the operating speed limit. The introduction of a well-designed structure improved the rise time from 12.6 µs to 115 ns, albeit at the expense of the responsivity, which decreased from 1.25 A W-1 to 0.56 A W-1. Similarly, the falling time was improved from 38 µs to 288 ns with a sacrifice in responsivity from 1.25 A W-1 to 0.29 A W-1, achieved through the introduction of Ge-induced defect-recombination centers within the well. Through a judicious well design and the introduction of recombination defect centers, the minimum pulse width could be improved from 50.6 µs to 435 ns, facilitating 2 MHz operation. This represents more than 100 times increase compared to previously reported graphene and graphene/Si hybrid photodetectors.
ABSTRACT
Sargassum horneri (SH) is widely consumed as a healthy seaweed food in the Asia-Pacific region. However, the bioactive components contributing to its biological activity remain unknown. Herein, we optimized multifrequency ultrasonic-assisted extraction conditions to achieve higher antioxidant activity using a response surface methodology and an artificial neural network. High-resolution mass spectrometry (HRMS; negative mode) was used to tentatively identify the secondary metabolites in the optimized SH extract, which were further tested against oxidative stress in RAW264.7 cells. Additionally, the identified compounds were analyzed in silico to determine their binding energies with the Keap1 protein (4L7B). We identified 89 compounds using HRMS, among which 19 metabolites (8 polyphenolics, 2 flavonoids, 2 lignans, 2 terpenes, 2 tannins, 2 sulfolipids, and 1 phospholipid) were putatively reported for the first time in SH. The in vitro results revealed that optimized SH extract inhibited oxidative stress via the Nrf2/MAPKs/HO-1 pathway in a dose-dependent manner. This result was validated by performing in silico simulation, indicating that sargaquinoic acid and glycitein-7-O-glucuronide had the highest binding energies (-9.20 and -9.52 Kcal/mol, respectively) toward Keap1 (4L7B). This study offers a unique approach for the scientific community to identify potential bioactive compounds by optimizing the multivariant extraction processing conditions, which could be used to develop functional and nutraceutical foods.
ABSTRACT
This study focuses on the identification and characterization of a glycoprotein from Sargassum fusiforme (Harvey) Setchell (SFGP), as well as investigating its potential anti-inflammatory properties both in vitro and in vivo, along with the underlying mechanism. SDS-PAGE analysis revealed a prominent band with a molecular weight of <10 kDa, consisting of 58.39 % protein and 41.61 % carbohydrates, which was confirmed through glycoprotein staining and Coomassie blue staining. Various analytical techniques, including high-resolution mass spectrometry (HRMS), FTIR, amino acid analysis, and UV-visible spectrometry, provided evidence for the presence of monosaccharides (such as d-glucose and mannose) and 17 amino acids linked by an O-glycopeptide bond. In vitro and in vivo studies were conducted to assess the anti-inflammatory activities of SFGP. The results demonstrated that SFGP effectively attenuated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-treated RAW264.7 cells. Moreover, SFGP administration significantly and dose-dependently suppressed TLR4/MyD88 signaling as well as the phosphorylation of MAPKs, IκB, and NF-κB, leading to a reduction in the production of TNF-α, IL-1ß, and IL-6 in LPS-stimulated RAW264.7 cells. Furthermore, the anti-inflammatory efficacy of SFGP was validated in a carrageenan-induced inflammatory mouse model. These findings indicate that SFGP exhibits anti-inflammatory characteristics and has the potential to be utilized as a novel anti-inflammatory agent.
Subject(s)
Anti-Inflammatory Agents , Glycoproteins , Myeloid Differentiation Factor 88 , NF-kappa B , Sargassum , Signal Transduction , Toll-Like Receptor 4 , Animals , Sargassum/chemistry , Toll-Like Receptor 4/metabolism , Mice , NF-kappa B/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Signal Transduction/drug effects , RAW 264.7 Cells , Myeloid Differentiation Factor 88/metabolism , Glycoproteins/pharmacology , Glycoproteins/chemistry , Cyclooxygenase 2/metabolism , Male , Lipopolysaccharides , Cytokines/metabolism , Nitric Oxide Synthase Type II/metabolism , Edible SeaweedsABSTRACT
Effect-directed analysis (EDA) is a crucial tool in environmental toxicology, effectively integrating toxicity testing with chemical analysis. The conventional EDA approach, however, presents challenges such as significant solvent consumption, extended analysis time, labor intensity, and potential contamination risks. In response, we introduce an innovative alternative to the conventional EDA. This method utilizes the MTT bioassay and online two-dimensional liquid chromatography (2D LC) coupled with high-resolution mass spectrometry (HR-MS), significantly reducing the fractionation steps and leveraging the enhanced sensitivity of the bioassay and automated chemical analysis. In the chemical analysis phase, a switching valve interface is employed for comprehensive analysis. We tested the performance of both the conventional and our online 2D LC-based methods using a household product. Both methods identified the same number of toxicants in the sample. Our alternative EDA is 22.5 times faster than the conventional method, fully automated, and substantially reduces solvent consumption. This novel approach offers ease, cost-effectiveness, and represents a paradigm shift in EDA methodologies. By integrating a sensitive bioassay with online 2D LC, it not only enhances efficiency but also addresses the challenges associated with traditional methods, marking a significant advancement in environmental toxicology research.
Subject(s)
Environmental Pollutants , Chromatography, Liquid/methods , Environmental Pollutants/toxicity , Environmental Pollutants/analysis , Toxicity Tests/methods , Environmental Monitoring/methods , Mass Spectrometry/methods , Biological Assay/methods , Ecotoxicology/methodsABSTRACT
This study sought to optimize the ultrasonic-assisted extraction of polyphenolic compounds from unmature Ajwa date seeds (UMS), conduct untargeted metabolite identification and assess antioxidant and depigmenting activities. Response surface methodology (RSM) utilizing the Box-Behnken design (BBD) and artificial neural network (ANN) modeling was applied to optimize extraction conditions, including the ethanol concentration, extraction temperature and time. The determined optimal conditions comprised the ethanol concentration (62.00%), extraction time (29.00 min), and extraction temperature (50 °C). Under these conditions, UMS exhibited total phenolic content (TPC) and total flavonoid content (TFC) values of 77.52 ± 1.55 mgGAE/g and 58.85 ± 1.12 mgCE/g, respectively, with low relative standard deviation (RSD%) and relative standard error (RSE%). High-resolution mass spectrometry analysis unveiled the presence of 104 secondary metabolites in UMS, encompassing phenols, flavonoids, sesquiterpenoids, lignans and fatty acids. Furthermore, UMS demonstrated robust antioxidant activities in various cell-free antioxidant assays, implicating engagement in both hydrogen atom transfer and single electron transfer mechanisms. Additionally, UMS effectively mitigated tert-butyl hydroperoxide (t-BHP)-induced cellular reactive oxygen species (ROS) generation in a concentration-dependent manner. Crucially, UMS showcased the ability to activate mitogen-activated protein kinases (MAPKs) and suppress key proteins including tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and -2) and microphthalmia-associated transcription factor (MITF), which associated melanin production in MNT-1 cell. In summary, this study not only optimized the extraction process for polyphenolic compounds from UMS but also elucidated its diverse secondary metabolite profile. The observed antioxidant and depigmenting activities underscore the promising applications of UMS in skincare formulations and pharmaceutical developments.
ABSTRACT
INTRODUCTION: Nymphaea rubra belongs to the Nymphaea family and is regarded as a vegetable used in traditional medicine to cure several ailments. These species are rich in phenolic acid, flavonoids, and hydrolysable tannin. OBJECTIVE: This study aimed to assess the biological activities of Nymphaea rubra flowers (NRF) and leaves (NRL) by identifying and quantifying their polyphenolic compounds using ultra-performance liquid chromatography coupled to quadrupole cyclic ion mobility time-of-flight mass spectrometry (UHPLC-Q-cIM-TOF-MS) and triple quadrupole mass spectrometry (UHPLC-TQ-MS). METHODOLOGY: NRF and NRL powder was extracted with methanol and fractionated using hexane, ethylacetate, and water. Antioxidant and α-glucosidase, and tyrosinase enzyme inhibitory activities were evaluated. The polyphenolic components of NRF and NRL were identified and quantified using UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS. The method was validated using linearity, precision, accuracy, limit of detection (LOD), and lower limit of quantification (LLOQ). RESULTS: Bioactive substances and antioxidants were highest in the ethylacetate fraction of flowers and leaves. Principal component analysis showed how solvent and plant components affect N. rubra's bioactivity and bioactive compound extraction. A total of 67 compounds were identified, and among them 21 significant polyphenols were quantified. Each calibration curve had R2 > 0.998. The LOD and LLOQ varied from 0.007 to 0.09 µg/mL and from 0.01 to 0.1 µg/mL, respectively. NRF contained a significant amount of gallic acid (10.1 mg/g), while NRL contained abundant pentagalloylglucose (2.8 mg/g). CONCLUSION: The developed method is simple, rapid, and selective for the identification and quantification of bioactive molecules. These findings provide a scientific basis for N. rubra's well-documented biological effects.
Subject(s)
Antioxidants , Flowers , Nymphaea , Plant Leaves , Polyphenols , Chromatography, High Pressure Liquid/methods , Plant Leaves/chemistry , Polyphenols/analysis , Flowers/chemistry , Antioxidants/analysis , Antioxidants/pharmacology , Nymphaea/chemistry , Mass Spectrometry/methods , Monophenol Monooxygenase/antagonists & inhibitors , Reproducibility of Results , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/analysis , alpha-Glucosidases/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/analysisABSTRACT
To investigate the effect of the predominant fungal species from Korean traditional meju and doenjang on soybean fermentation, the enzymatic activity and amino acid production of twenty-two fungal strains were assessed through solid- and liquid-state soybean fermentation. Enzymatic activity analyses of solid-state fermented soybeans revealed different enzyme activities involving protease, leucine aminopeptidase (LAP), carboxypeptidase (CaP), glutaminase, γ-glutamyl transferase (GGT), and amylase, depending on the fungal species. These enzymatic activities significantly affected the amino acid profile throughout liquid-state fermentation. Strains belonging to Mucoromycota, including Lichtheimia, Mucor, Rhizomucor, and Rhizopus, produced smaller amounts of total amino acids and umami-producing amino acids, such as glutamic acid and aspartic acid, than strains belonging to Aspergillus subgenus circumdati. The genera Penicillium and Scopulariopsis produced large amounts of total amino acids and glutamic acid, suggesting that these genera play an essential role in producing umami and kokumi tastes in fermented soybean products. Strains belonging to Aspergillus subgenus circumdati, including A. oryzae, showed the highest amino acid content, including glutamic acid, suggesting the potential benefits of A. oryzae as a starter for soybean fermentation. This study showed the potential of traditional meju strains as starters for soybean fermentation. However, further analysis of processes such as the production of G-peptide for kokumi taste and volatile compounds for flavor and safety is needed.
Subject(s)
Amino Acids , Soy Foods , Amino Acids/metabolism , Soy Foods/microbiology , Glycine max , Fermentation , Fungi , Aspergillus/metabolism , Glutamic Acid/metabolism , Peptide Hydrolases/metabolismABSTRACT
AIM: This study aimed to develop and validate the effectiveness of a hybrid simulation education program designed to enhance the forensic nursing competency of emergency department nurses. BACKGROUND: Emergency nurses often bear the responsibility of conducting forensic nursing assessments and interventions, such as patient recognition and evidence collection, to safeguard patients' legal rights, given their frequent encounters with emergency department patients. Simulation methods have proven effective in training for forensic nursing care. However, there is still a need for the development of forensic nursing education using simulation methods. DESIGN: This study employed a one-group pre-test/post-test quasi-experimental design. A four-hour simulation education program was developed based on the analysis, design, development, implementation, and evaluation model, with a focus on enhancing forensic nursing competency. METHODS: Nurses with more than six months of clinical experience in the emergency department in South Korea were divided into an experimental group (n=23) and a baseline comparison group (n=24). Both groups completed self-evaluations of their forensic nursing competency through a survey. The experimental group underwent the simulation education program, and their forensic nursing performance was evaluated before and after the program. Following the training, participants completed a questionnaire to assess their forensic nursing competency and satisfaction with the program. RESULTS: The initial forensic nursing competency of the experimental and baseline comparison groups was found to be similar. However, the forensic nursing competency and performance of the experimental group exhibited significant improvement after the training. Regarding program evaluation, the average scores on a 5-point scale were as follows: theoretical lecture (4.79â¯SD 0.27), simulation education (4.78â¯SD 0.29), simulation design (4.42â¯SD 0.45), and satisfaction with the educational program (4.82â¯SD 0.28). CONCLUSIONS: The forensic nursing competency-based simulation education program herein improved the relevant competency and performance of emergency nurses.
Subject(s)
Forensic Nursing , Research Design , Humans , Competency-Based Education , Curriculum , Clinical Competence , Program EvaluationABSTRACT
Despite achievements in the remarkable photoelectrochemical (PEC) performance of photoelectrodes based on organometal halide perovskites (OHPs), the scaling up of small-scale OHP-based PEC systems to large-scale systems remains a great challenge for their practical application in solar water splitting. Significant resistive losses and intrinsic defects are major obstacles to the scaling up of OHP-based PEC systems, leading to the PEC performance degradation of large-scale OHP photoelectrodes. Herein, a scalable design of the OHP-based PEC systems by modularization of the optimized OHP photoelectrodes exhibiting a high solar-to-hydrogen conversion efficiency of 10.4% is suggested. As a proof-of-concept, the OHP-based PEC module achieves an optimal PEC performance by avoiding major obstacles in the scaling up of the OHP photoelectrodes. The constructed OHP module is composed of a total of 16 OHP photoelectrodes, and a photocurrent of 11.52 mA is achieved under natural sunlight without external bias. The successful operation of unassisted solar water splitting using the OHP module without external bias can provide insights into the design of scalable OHP-based PEC systems for future practical application and commercialization.
ABSTRACT
The date palm (Phoenix dactylifera L.) is a popular edible fruit consumed all over the world and thought to cure several chronic diseases and afflictions. The profiling of the secondary metabolites of optimized ripe Ajwa date pulp (RADP) extracts is scarce. The aim of this study was to optimize the heat extraction (HE) of ripe Ajwa date pulp using response surface methodology (RSM) and artificial neural network (ANN) modeling to increase its polyphenolic content and antioxidant activity. A central composite design was used to optimize HE to achieve the maximum polyphenolic compounds and antioxidant activity of target responses as a function of ethanol concentration, extraction time, and extraction temperature. From RSM estimates, 75.00% ethanol and 3.7 h (extraction time), and 67 °C (extraction temperature) were the optimum conditions for generating total phenolic content (4.49 ± 1.02 mgGAE/g), total flavonoid content (3.31 ± 0.65 mgCAE/g), 2,2-diphenyl-1-picrylhydrazyl (11.10 ± 0.78 % of inhibition), and cupric-reducing antioxidant capacity (1.43 µM ascorbic acid equivalent). The good performance of the ANN was validated using statistical metrics. Seventy-one secondary metabolites, including thirteen new bioactive chemicals (hebitol II, 1,2-di-(syringoyl)-hexoside, naringin dihydrochalcone, erythron-guaiacylglycerol-ß-syringaresinol ether hexoside, erythron-1-(4'-O-hexoside-3,5-dimethoxyphenyl)-2-syrngaresinoxyl-propane-1,3-diol, 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid, linustatin and 1-deoxynojirimycin galactoside), were detected using high-resolution mass spectroscopy. The results revealed a significant concentration of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.
ABSTRACT
The conversion of glycerol to high-value-added products via photoelectrochemical (PEC) oxidation has emerged as a promising approach for utilizing a sustainable and clean energy source with environmental and economic benefits. Moreover, the energy requirement for glycerol to produce hydrogen is lower than that for pure water splitting. In this study, we propose the use of WO3 nanostructures decorated with Bi-based metal-organic frameworks (Bi-MOFs) as the photoanode for glycerol oxidation with simultaneous hydrogen production. The WO3-based electrodes selectively converted glycerol to glyceraldehyde, a high-value-added product, with remarkable selectivity. The Bi-MOF-decorated WO3 nanorods enhanced the surface charge transfer and adsorption properties, thereby improving the photocurrent density and production rate (1.53 mA/cm2 and 257 mmol/m2·h at 0.8 VRHE). The photocurrent was maintained for 10 h, ensuring stable glycerol conversion. Furthermore, at 1.2 VRHE, the average production rate of glyceraldehyde reached 420 mmol/m2·h, with a selectivity of 93.6% between beneficial oxidized products over the photoelectrode. This study provides a practical approach for the conversion of glycerol to glyceraldehyde via the selective oxidation of WO3 nanostructures and demonstrates the potential of Bi-MOFs as a promising cocatalyst for PEC biomass valorization.
ABSTRACT
INTRODUCTION: Sargassum fusiforme (Harvey) Setchell, also known as Tot (in Korean) and Hijiki (in Japanese), is widely consumed in Korea, Japan, and China due to its health promoting properties. However, the bioactive component behind the biological activity is still unknown. OBJECTIVES: We aimed to optimise the extraction conditions for achieving maximum tyrosinase inhibition activity by using two sophisticated statistical tools, that is, response surface methodology (RSM) and artificial neural network (ANN). Moreover, high-resolution mass spectrometry (HRMS) was used to tentatively identify the components, which are then further studied for molecular docking study using 2Y9X protein. METHODOLOGY: RSM central composite design was used to conduct extraction using microwave equipment, which was then compared to ANN. Electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was used to tentatively identify bioactive components, which were then docked to the 2Y9X protein using AutoDock Vina and MolDock software. RESULTS: Maximum tyrosinase inhibition activity of 79.530% was achieved under optimised conditions of time: 3.27 min, temperature: 128.885°C, ethanol concentration: 42.13%, and microwave intensity: 577.84 W. Furthermore, 48 bioactive compounds were tentatively identified in optimised Sargassum fusiforme (OSF) extract, and among them, seven phenolics, five flavonoids, five lignans, six terpenes, and five sulfolipids and phospholipids were putatively reported for the first time in Sargassum fusiforme. Among 48 bioactive components, trifuhalol-A, diphlorethohydroxycarmalol, glycyrrhizin, and arctigenin exhibited higher binding energies for 2Y9X. CONCLUSION: Taken together, these findings suggest that OSF extract can be used as an effective skin-whitening source on a commercial level and could be used in topical formulations by replacing conventional drugs.
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This study investigated the chemicals extracted from an EPS buoy used in aquaculture, which were subsequently collected from a recycling center. It was observed that the chemicals generated upon photodegradation make disposed buoys more toxic. Analysis of the extracted chemicals revealed the presence of 37 compounds, with four compounds quantitatively determined. Further analysis showed that the quantity of compounds dissolved in seawater was significantly higher than the amount remaining on the buoy surface. Based on the assumption that the buoy was exposed to sunlight for a year, it was estimated that 14.44 mg of the four compounds dissolved into the ocean. Given that South Korea used over 7 million EPS buoys, photodegraded EPS buoys are expected to represent a significant source of potentially hazardous chemicals.
Subject(s)
Polystyrenes , Seawater , Polystyrenes/analysis , Photolysis , Seawater/chemistry , Aquaculture , Republic of KoreaABSTRACT
A high dependence on aerobic glycolysis, known as the Warburg effect, is one of the metabolic features exhibited by tumor cells. Therefore, targeting glycolysis is becoming a very promising strategy for the development of anticancer drugs. In the present study, it was investigated whether preadaptation of malignant mesothelioma (MM) cells to an acidic environment was associated with a metabolic shift to the Warburg phenotype in energy production, and whether apigenin targets acidosisdriven metabolic reprogramming. Cell viability, glycolytic activity, Annexin VPE binding activity, reactive oxygen species (ROS) levels, mitochondrial membrane potential, ATP content, western blot analysis and spheroid viability were assessed in the present study. MM cells preadapted to lactic acid were resistant to the anticancer drug gemcitabine, increased Akt activation, downregulated p53 expression, and upregulated ratelimiting enzymes in glucose metabolism compared with their parental cells. Apigenin treatment increased cytotoxicity, Akt inactivation and p53 upregulation. Apigenin also reduced glucose uptake along with downregulation of key regulatory enzymes in glycolysis, increased ROS levels with loss of mitochondrial membrane potential, and downregulated the levels of complexes I, III and IV in the mitochondrial electron transport chain with intracellular ATP depletion, resulting in upregulation of molecules mediating apoptosis and necroptosis. Apigenininduced alterations of cellular responses were similar to those of Akt inactivation by Ly294002. Overall, the present results provide mechanistic evidence supporting the antiglycolytic and cytotoxic role of apigenin via inhibition of the PI3K/Akt signaling pathway and p53 upregulation.
Subject(s)
Mesothelioma, Malignant , Mesothelioma , Humans , Up-Regulation , Proto-Oncogene Proteins c-akt/metabolism , Apigenin/pharmacology , Apigenin/therapeutic use , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Reactive Oxygen Species/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Necroptosis , Mesothelioma/drug therapy , Mesothelioma/genetics , Mesothelioma/pathology , Apoptosis , Glycolysis , Adenosine Triphosphate/metabolismABSTRACT
We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.
Subject(s)
COVID-19 , Epilepsy , Multiple Sclerosis , Humans , Male , Young Adult , COVID-19/complications , COVID-19 Vaccines/adverse effects , Death, Sudden/etiology , Epilepsy/complications , Multiple Sclerosis/complications , Seizures/complications , Vaccination/adverse effects , Fatal OutcomeABSTRACT
Each individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (Piper betle L.) extract (PBL) and the underlying mechanism. Ethyl acetate fractions of PBL (PBLA) demonstrated excellent phenolic content (342 ± 4.02 mgGAE/g) and strong DPPH, ABTS radicals, and nitric oxide (NO) scavenging activity with an IC50 value of 41.52 ± 1.02 µg/mL, 45.60 ± 0.56 µg/mL, and 51.42 ± 1.25 µg/mL, respectively. Contrarily, ethanolic extract of PBL (PBLE) showed potent mushroom, mice, and human tyrosinase inhibition activity (IC50 = 7.72 ± 0.98 µg/mL, 20.59 ± 0.83 µg/mL and 24.78 ± 0.56 µg/mL, respectively). According to gas chromatography-mass spectrometry, PBL is abundant in caryophyllene, eugenol, O-eugenol, 3-Allyl-6-methoxyphenyl acetate, and chavicol. An in vitro and in vivo investigation showed that PBLE suppressed tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and Trp-2), and microphthalmia-associated transcription factors (MITF), decreasing the formation of melanin in contrast to the untreated control. PBLE reduced the cyclic adenosine monophosphate (cAMP) response to an element-binding protein (CREB) phosphorylation by preventing the synthesis of cAMP. Additionally, it activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38), destroying Tyr and MITF and avoiding melanin production. Higher levels of microtubule-associated protein-light chain 3 (LC3-II), autophagy-related protein 5 (Atg5), Beclin 1, and lower levels of p62 demonstrate that PBLE exhibits significant anti-melanogenic effects via an autophagy-induction mechanism, both in vitro and in vivo. Additionally, PBLE significantly reduced the amount of lipid peroxidation while increasing the activity of several antioxidant enzymes in vivo, such as catalase, glutathione, superoxide dismutase, and thioredoxin. PBLE can therefore be employed in topical formulations as a potent skin-whitening agent.
ABSTRACT
Boosting dielectric permittivity representing electrical polarizability of dielectric materials has been considered a keystone for achieving scientific breakthroughs as well as technological advances in various multifunctional devices. Here, we demonstrate sizable enhancements of low-frequency dielectric responses in oxygen-deficient oxide ceramics through specific treatments under humid environments. Ultrahigh dielectric permittivity (~5.2 × 106 at 1 Hz) is achieved by hydrogenation, when Ni-substituted BaTiO3 ceramics are exposed to high humidity. Intriguingly, thermal annealing can restore the dielectric on-state (exhibiting huge polarizability in the treated ceramics) to the initial dielectric off-state (displaying low polarizability of ~103 in the pristine ceramics after sintering). The conversion between these two dielectric states via the ambient environment-mediated treatments and the successive application of external stimuli allows us to realize reversible control of dielectric relaxation characteristics in oxide ceramics. Conceptually, our findings are of practical interest for applications to highly efficient dielectric-based humidity sensors.
ABSTRACT
The Ajwa date (Phoenix dactylifera L., Arecaceae family) is a popular edible fruit consumed all over the world. The profiling of the polyphenolic compounds of optimized unripe Ajwa date pulp (URADP) extracts is scarce. The aim of this study was to extract polyphenols from URADP as effectively as possible by using response surface methodology (RSM). A central composite design (CCD) was used to optimize the extraction conditions with respect to ethanol concentration, extraction time, and temperature and to achieve the maximum amount of polyphenolic compounds. High-resolution mass spectrometry was used to identify the URADP's polyphenolic compounds. The DPPH-, ABTS-radical scavenging, α-glucosidase, elastase and tyrosinase enzyme inhibition of optimized extracts of URADP was also evaluated. According to RSM, the highest amounts of TPC (24.25 ± 1.02 mgGAE/g) and TFC (23.98 ± 0.65 mgCAE/g) were obtained at 52% ethanol, 81 min time, and 63 °C. Seventy (70) secondary metabolites, including phenolic, flavonoids, fatty acids, and sugar, were discovered using high-resolution mass spectrometry. In addition, twelve (12) new phytoconstituents were identified for the first time in this plant. Optimized URADP extract showed inhibition of DPPH-radical (IC50 = 87.56 mg/mL), ABTS-radical (IC50 = 172.36 mg/mL), α-glucosidase (IC50 = 221.59 mg/mL), elastase (IC50 = 372.25 mg/mL) and tyrosinase (IC50 = 59.53 mg/mL) enzymes. The results revealed a significant amount of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.