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Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024This study aims to systematically evaluate the protective role of quercetin (QCT), a naturally occurring flavonoid, against oxidative damage in human endometrial stromal...
OBJECTIVE
This study aims to systematically evaluate the protective role of quercetin (QCT), a naturally occurring flavonoid, against oxidative damage in human endometrial stromal cells (HESCs) induced by hydrogen peroxide (HO). Oxidative stress, such as that induced by HO, is known to contribute significantly to cellular damage and has been implicated in various reproductive health issues. The study is focused on investigating how QCT interacts with specific molecular pathways to mitigate this damage. Special attention was given to the p38 MAPK/NOX4 signaling pathway, which is crucial to the regulation of oxidative stress responses in cellular systems. By elucidating these mechanisms, the study seeks to confirm the potential of QCT not only as a protective agent against oxidative stress but also as a therapeutic agent that could be integrated in treatments of conditions characterized by heightened oxidative stress in endometrial cells.
METHODS
cultures of HESCs were treated with QCT at different concentrations (0, 10, 20, and 40 μmol/L) for 24 h to verify the non-toxic effects of QCT on normal endometrial cells. Subsequently, 250 μmol/L HO was used to incubate the cells for 12 h to establish an HO-induced HESCs injury model. HESCs were pretreated with QCT for 24 h, which was followed by stimulation with HO. Then, CCK-8 assay was performed to examine the cell viability and to screen for the effective intervention concentration. HESCs were divided into 3 groups, the control group, the HO model group, and the HO+QCT group. Intracellular levels of reactive oxygen species (ROS) were precisely quantified using the DCFH-DA fluorescence assay, a method known for its accuracy in detecting and quantifying oxidative changes within the cell. The mitochondrial membrane potential was determined by JC-1 staining. Annexin Ⅴ/PI double staining and flow cytometry were performed to determine the effect of QCT on HO-induced apoptosis of HESCs. Furthermore, to delve deeper into the cellular mechanisms underlying the observed effects, Western blot analysis was conducted to measure the expression levels of the critical proteins involved in oxidative stress response, including NADPH oxidase 4 (NOX4), p38 mitogen-activated protein kinase (p38 MAPK), and phosphorylated p38 MAPK (p-p38 MAPK). This analysis helps increase understanding of the specific intracellular signaling pathways affected by QCT treatment, giving special attention to its potential for modulation of the p38 MAPK/NOX4 pathway, which plays a significant role in cellular defense mechanisms against oxidative stress.
RESULTS
In this study, we started off by assessing the toxicity of QCT on normal endometrial cells. Our findings revealed that QCT at various concentrations (0, 10, 20, and 40 μmol/L) did not exhibit any cytotoxic effects, which laid the foundation for further investigation into its protective roles. In the HO-induced HESCs injury model, a significant reduction in cell viability was observed, which was linked to the generation of ROS and the resultant oxidative damage. However, pretreatment with QCT (10 μmol/L and 20 μmol/L) significantly enhanced cell viability after 24 h (<0.05), with the 20 μmol/L concentration showing the most substantial effect. This suggests that QCT can effectively reverse the cellular damage caused by HO. Furthermore, the apoptosis assays demonstrated a significant increase in the apoptosis rates in the HO model group compared to those in the control group (<0.01). However, co-treatment with QCT significantly reversed this trend (<0.05), indicating QCT's potential protective role in mitigating cell apoptosis. ROS assays showed that, compared to that in the control group, the average fluorescence intensity of ROS in the HO model group significantly increased (<0.01). QCT treatment significantly reduced the ROS fluorescence intensity in the HO+QCT group compared to the that in the HO model group, suggesting an effective alleviation of oxidative damage (<0.05). JC-1 staining for mitochondrial membrane potential changes revealed that compared to that in the control, the proportion of cells with decreased mitochondrial membrane potential significantly increased in the HO model group (<0.01). However, this proportion was significantly reduced in the QCT-treated group compared to that of the HO model group (<0.05). Finally, Western blot analysis indicated that the expression levels of NOX4 and p-p38 MAPK proteins were elevated in the HO model group compared to those of the control group (<0.05). Following QCT treatment, these protein levels significantly decreased compared to those of the HO model group (<0.05). These results suggest that QCT may exert its protective effects against oxidative stress by modulating the p38 MAPK/NOX4 signaling pathway.
CONCLUSION
QCT has demonstrated significant protective effects against HO-induced oxidative damage in HESCs. This protection is primarily achieved through the effective reduction of ROS accumulation and the inhibition of critical signaling pathways involved in the oxidative stress response, notably the p38 MAPK/NOX4 pathway. The results of this study reveal that QCT's ability to modulate these pathways plays a key role in alleviating cellular damage associated with oxidative stress conditions. This indicates not only its potential as a protective agent against cellular oxidative stress, but also highlights its potential for therapeutic applications in treating conditions characterized by increased oxidative stress in the endometrium, thereby offering the prospect of enhancing reproductive health. Future studies should explore the long-term effects of QCT and its clinical efficacy , thereby providing a clear path toward its integration into therapeutic protocols.
Topics: Humans; Hydrogen Peroxide; Oxidative Stress; Female; NADPH Oxidase 4; Quercetin; Endometrium; p38 Mitogen-Activated Protein Kinases; Stromal Cells; Signal Transduction; Reactive Oxygen Species; Apoptosis; Cells, Cultured
PubMed: 38948281
DOI: 10.12182/20240560107 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024To investigate the effect of Sanshentongmai (SSTM) mixture on the regulation of oxidative damage to rat cardiomyocytes (H9C2) through microRNA-146a and its mechanism.
OBJECTIVE
To investigate the effect of Sanshentongmai (SSTM) mixture on the regulation of oxidative damage to rat cardiomyocytes (H9C2) through microRNA-146a and its mechanism.
METHODS
H9C2 were cultured , HO was used as an oxidant to create an oxidative damage model in H9C2 cells. SSTM intervention was administered to the H9C2 cells. Then, the changes in HO-induced oxidative damage in H9C2 cells and the expression of microRNA-146a were observed to explore the protective effect of SSTM on H9C2 and its mechanism. H9C2 cells cultured were divided into 3 groups, including a control group, a model group of HO-induced oxidative damage (referred to hereafter as the model group), and a group given HO modeling plus SSTM intervention at 500 μg/L for 72 h (referred to hereafter as the treatment group). The cell viability was measured by CCK8 assay. In addition, the levels of N-terminal pro-brain natriuretic peptide (Nt-proBNP), nitric oxide (NO), high-sensitivity C-reactive protein (Hs-CRP), and angiotensin were determined by enzyme-linked immunosorbent assay (ELISA). The expression level of microRNA-146a was determined by real-time PCR (RT-PCR).
RESULT
H9C2 cells were pretreated with SSTM at mass concentrations ranging from 200 to 1500 μg/L. Then, CCK8 assay was performed to measure cell viability and the findings showed that the improvement in cell proliferation reached its peak when the mass concentration of SSTM was 500 μg/L, which was subsequently used as the intervention concentration. ELISA was performed to measure the indicators related to heart failure, including Nt-proBNP, NO, Hs-CRP, and angiotensin Ⅱ. Compared with those of the control group, the expressions of Nt-proBNP and angiotensin Ⅱ in the treatment group were up-regulated (<0.05), while the expression of NO was down-regulated (<0.05). There was no significant difference in the expression of Hs-CRP between the treatment group and the control group. These findings indicate that SSTM could effectively ameliorate oxidative damage in H9C2 rat cardiomyocytes. Finally, according to the RT-PCR findings for the expression of microRNA-146a in each group, HO treatment at 15 μmol/L could significantly reduce the expression of microRNA-146a, and the expression of microRNA-146a in the treatment group was nearly doubled compared with that in the model group. There was no significant difference between the treatment group and the control group.
CONCLUSION
SSTM can significantly resist the HO-induced oxidative damage of H9C2 cells and may play a myocardial protective role by upregulating microRNA-146a.
Topics: Myocytes, Cardiac; Animals; MicroRNAs; Rats; Oxidative Stress; Hydrogen Peroxide; Drugs, Chinese Herbal; Up-Regulation; Cell Survival; Cell Line; Drug Combinations
PubMed: 38948270
DOI: 10.12182/20240560601 -
PeerJ 2024Leaf inclination angle (LIA) and tillering impact the winter wheat ( L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield...
Leaf inclination angle (LIA) and tillering impact the winter wheat ( L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield can guide water-saving strategies through population control. In this study, six near-isogenic lines (NILs) and their parents were selected as materials. These special materials were characterized by varying tillering at the current sowing density, a similar genetic background, and, particularly, a gradient in mean flag leaf LIA. The investigation focused on the jointing to early grain-filling stage, the peak water requirement period of wheat crops. Population-scale transpiration (PT) and evaporation from the soil surface (E) were partitioned from total evapotranspiration (ET) by the means of micro-lysimeters. The results showed decreased PT, E, and ET with increased population density (PD) within a narrow density range derived from varying tillering across genotypes. Significant correlations existed between PD and ET, E, and PT, especially in the wettest 2017-2018 growing season. Within such narrow PD range, all the correlations between WU parameters and PD were negative, although some correlations were not statistically significant, thereby suggesting the population structure's predominant impact. No significant correlation existed between LIA and both ET and PT within the LIA range of 35°-65°. However, significant correlations occurred between LIA and E in two growing seasons. Genotypes with similar LIA but different PD produced varied ET; while with similar PD, the four pairs of genotypes with different LIA each consumed similar ET, thus highlighting PD's more crucial role in regulating ET. The yield increased with higher LIA, and showed a significant correlation, emphasizing the LIA's significant effect on yield. However, no correlation was observed with PD, indicating the minor effect of tillering at the current sowing density. Therefore these results might offer valuable insights for breeding water-saving cultivars and optimizing population structures for effective field water conservation.
Topics: Triticum; Plant Leaves; Plant Transpiration; Soil; Seasons; Water; Genotype
PubMed: 38948218
DOI: 10.7717/peerj.17618 -
PeerJ 2024Tolerance against acute warming is an essential trait that can determine how organisms cope during heat waves, yet the mechanisms underlying it remain elusive. Water...
Tolerance against acute warming is an essential trait that can determine how organisms cope during heat waves, yet the mechanisms underlying it remain elusive. Water salinity has previously been suggested to modulate warming tolerance in fish and may therefore provide clues towards these limiting mechanisms. Here, using the critical thermal maximum (CT) test, we investigated whether short (2 hours) and long (10 days) term exposure to different water salinities (2 hours: 0-5 ppt, 10 days: 0-3 ppt) affected acute warming tolerance in zebrafish ( = 263). We found that water salinity did not affect the warming tolerance of zebrafish at either time point, indicating that salinity does not affect the mechanism limiting acute warming tolerance in zebrafish at these salinity ranges, and that natural fluctuations in salinity levels might not have a large impact on acute warming tolerance in wild zebrafish.
Topics: Zebrafish; Animals; Salinity; Hot Temperature; Thermotolerance; Water
PubMed: 38948212
DOI: 10.7717/peerj.17343 -
Frontiers in Chemistry 20245-Hydroxymethylfurfural (HMF), serving as a versatile platform compound bridging biomass resource and the fine chemicals industry, holds significant importance in... (Review)
Review
5-Hydroxymethylfurfural (HMF), serving as a versatile platform compound bridging biomass resource and the fine chemicals industry, holds significant importance in biomass conversion processes. The electrooxidation of HMF plays a crucial role in yielding the valuable product (2,5-furandicarboxylic acid), which finds important applications in antimicrobial agents, pharmaceutical intermediates, polyester synthesis, and so on. Defect engineering stands as one of the most effective strategies for precisely synthesizing electrocatalytic materials, which could tune the electronic structure and coordination environment, and further altering the adsorption energy of HMF intermediate species, consequently increasing the kinetics of HMF electrooxidation. Thereinto, the most routine and effective defect are the anionic vacancies and cationic vacancies. In this concise review, the catalytic reaction mechanism for selective HMF oxidation is first elucidated, with a focus on the synthesis strategies involving both anionic and cationic vacancies. Recent advancements in various catalytic oxidation systems for HMF are summarized and synthesized from this perspective. Finally, the future research prospects for selective HMF oxidation are discussed.
PubMed: 38947956
DOI: 10.3389/fchem.2024.1416329 -
ACS Omega Jun 2024An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in DO with...
An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in DO with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters' α-C-H bond.
PubMed: 38947810
DOI: 10.1021/acsomega.3c09974 -
Cureus May 2024A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient...
A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient settings. However, its occurrence in hospitalized patients, particularly those with end-stage renal disease (ESRD), remains underreported. We present a case of a 74-year-old female with ESRD on hemodialysis who developed HAGMA highly suspicious for 5-oxoproline toxicity from acetaminophen usage following cardiac surgery. Despite a standard analgesic dose, the patient's renal impairment likely predisposed her to 5-oxoproline accumulation, resulting in severe metabolic acidosis. Discontinuation of acetaminophen led to the resolution of HAGMA, highlighting the importance of recognizing this rare but potentially life-threatening complication in the inpatient and critical care setting. This case suggests a potential interaction between acetaminophen metabolism and renal dysfunction in the pathogenesis of 5-oxoproline-induced HAGMA.
PubMed: 38947688
DOI: 10.7759/cureus.61328 -
ACS Central Science Jun 2024Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been a...
Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been a longstanding challenge. To overcome the delivery barrier, we explored a reversible, bioconjugation-based approach to modify the surface charge of protein cargos with an anionic "cloak" to facilitate electrostatic complexation and delivery with lipid nanoparticle (LNP) formulations. We demonstrate that the conjugation of lysine-reactive sulfonated compounds can allow for the delivery of various protein cargos using FDA-approved LNP formulations of the ionizable cationic lipid DLin-MC3-DMA (MC3). We apply this strategy to functionally deliver RNase A for cancer cell killing as well as a full-length antibody to inhibit oncogenic β-catenin signaling. Further, we show that LNPs encapsulating cloaked fluorescent proteins distribute to major organs in mice following systemic administration. Overall, our results point toward a generalizable platform that can be employed for intracellular delivery of a wide range of protein cargos.
PubMed: 38947210
DOI: 10.1021/acscentsci.4c00071 -
RSC Advances Jun 2024A new eco-friendly method for creating an optical sensor membrane specifically designed to detect yttrium ions (Y) has been developed. The proposed sensor membrane is...
A new eco-friendly method for creating an optical sensor membrane specifically designed to detect yttrium ions (Y) has been developed. The proposed sensor membrane is fabricated by integrating 4-(2-arsonophenylazo) salicylic acid (APASA), sodium tetraphenylborate (Na-TPB), and tri--octyl phosphine oxide (TOPO) into a plasticized poly(vinyl chloride) matrix with dimethyl sebacate (DMS) as the plasticizer. In this sensor membrane, APASA functions dually as an ionophore and a chromoionophore, while TOPO enhances the complexation of Y ions with APASA. The composition of the sensor membrane has been meticulously optimized to achieve peak performance. The current membrane exhibits a linear dynamic range for Y ions from 8.0 × 10 to 2.3 × 10 M, with detection and quantification limits of 2.3 × 10 and 7.7 × 10 M, respectively. No interference from other potentially interfering cations and anions was observed in the determination of Y. The membrane showed strong stability and a swift response time of about 3.0 minutes, with no signs of APASA leaching. This sensor is highly selective for Y ions and can be renewed by treating it with 0.15 M HNO. It has been effectively applied to measure Y in nickel-based alloys, as well as in biological and environmental samples.
PubMed: 38946767
DOI: 10.1039/d4ra03854a -
Journal of Oleo Science 2024The objective of this research was to evaluate the efficiency of aqueous enzymatic extraction (AEE) to obtain oil from hemp seeds (Cannabis sativa L.) grown in northern...
Combined Effect of Protease, Hemicellulase and Pectinase on the Quality of Hemp Seed Oil (Cannabis sativa L.) Obtained by Aqueous Enzymatic Extraction as an Eco-friendly Method.
The objective of this research was to evaluate the efficiency of aqueous enzymatic extraction (AEE) to obtain oil from hemp seeds (Cannabis sativa L.) grown in northern Morocco. Optimisation of AEE extraction parameters, including pH, enzyme concentration (hemicellulase, protease and pectinase), temperature and incubation time, to maximize oil yield was achieved using response surface methodology with a central composite design. For comparison, the solvent extraction (Soxhlet) (SE) method was also used. Optimized hydrolysis conditions involved incubation for 4 hours at 60°C with a pH of 6.5, using a multi-enzyme preparation comprising protease, hemicellulase and pectinase at concentrations of 55, 202.5 and 234 U/mg, respectively. Referring to the conventional Soxhlet extraction (SE), Aqueous Enzymatic Extraction (AEE) achieved a 30.65% oil recovery rate under the optimized parameters mentioned above. The use of enzymes produced an oil that was more stable against oxidation than the solvent-extracted oil, with a peroxide value (PV) of 19.54 and 47.87 meq O /kg, respectively. Furthermore, HPLC-DAD analysis of tocopherol content indicated a higher total tocopherol content (547.2 mg/kg) in Aqueous Enzymatic Extraction (AEE) compared to Soxhlet Extraction (SE) (513.51 mg/kg), with γ-tocopherol being the predominant form. No significant differences in fatty acid composition were observed between the two extraction methods with linoleic acid and alpha-linolenic acid being the predominant constituents.
Topics: Cannabis; Polygalacturonase; Plant Oils; Glycoside Hydrolases; Seeds; Peptide Hydrolases; Hydrolysis; Liquid-Liquid Extraction; Food Quality; Water; Tocopherols; Hydrogen-Ion Concentration; Temperature; Solvents; Green Chemistry Technology
PubMed: 38945925
DOI: 10.5650/jos.ess24031