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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 -
PeerJ 2024In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy...
In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized using neem leaf aqueous extracts and characterized using transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-Vis), and dynamic light scattering (DLS). Then compare its efficacy as anticancer and antibacterial agents with chemically synthesized ZnO-NPs and the neem leaf extract used for the green synthesis of ZnO-NPs. The TEM, UV-vis, and particle size confirmed that the developed ZnO-NPs are nanoscale. The chemically and greenly synthesized ZnO-NPs showed their optical absorbance at 328 nm and 380 nm, respectively, and were observed as spherical particles with a size of about 85 nm and 62.5 nm, respectively. HPLC and GC-MS were utilized to identify the bioactive components in the neem leaf aqueous extract employed for the eco-friendly production of ZnO-NPs. The HPLC analysis revealed that the aqueous extract of neem leaf contains 19 phenolic component fractions. The GC-MS analysis revealed the existence of 21 bioactive compounds. The antiproliferative effect of green ZnO-NPs was observed at different concentrations (31.25 µg/mL-1000 µg/mL) on Hct 116 and A 549 cancer cells, with an IC50 value of 111 µg/mL for A 549 and 118 µg/mL for Hct 116. On the other hand, the antibacterial activity against gram-positive and gram-negative bacteria was estimated. The antibacterial result showed that the MIC of green synthesized ZnO-NPs against gram-positive and gram-negative bacteria were 5, and 1 µg/mL. Hence, they could be utilized as effective antibacterial and antiproliferative agents.
Topics: Zinc Oxide; Anti-Bacterial Agents; Plant Extracts; Humans; Plant Leaves; Antineoplastic Agents; Azadirachta; Metal Nanoparticles; Microbial Sensitivity Tests; Green Chemistry Technology; Particle Size; Cell Line, Tumor
PubMed: 38948224
DOI: 10.7717/peerj.17588 -
Avicenna Journal of Phytomedicine 2024Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has...
OBJECTIVE
Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity.
MATERIALS AND METHODS
PC12 cells were treated with TSC and BMPC (1.95, 3.9, 7.81, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 μM) for 24 hr. ACR was then added at a concentration of 6.5 mM (IC), and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. In the study, male Wistar rats were treated with ACR (50 mg/kg, intraperitoneal (i.p.)) for 11 days alone or in combination with TSC and BMPC (2.5, 5, and 10 mg/kg, i.p.) or vitamin E (200 IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement.
RESULTS
studies showed that TSC at a concentration of 7.81 μM and BMPC at concentrations of 3.9, 7.81, and 15.62 μM exhibited the lowest toxicity in acrylamide administration. In the study, pretreatment with 2.5, 5, and 10 mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by 2.5, 5, and 10 mg/kg TSC and 2.5 mg/kg BMPC.
CONCLUSION
TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.
PubMed: 38948176
DOI: 10.22038/AJP.2023.22316 -
Clinical Interventions in Aging 2024Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between...
Malondialdehyde and Zinc May Relate to Severity of Microvascular Complications in Diabetes: A Preliminary Study on Older Adults with Type 2 Diabetes Mellitus in Northeast China.
BACKGROUND
Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults.
METHODS
The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated.
RESULTS
There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (). Iron (r = 0.147, r = 0.180, r = 0.193, ) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (r = -0.146, ). Magnesium was positively correlated with SOD (r = 0.147, ). Zinc (r = 0.616, r = 0.575, ) was positively correlated with SOD and T-AOC. Zinc (r =-0.636, r=-0.616, ) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], ), FBG (1.265, [1.059; 1.511], ), HbAlc (1.545, [1.431; 1.680], P <0.01), MDA (2.989, [1.900; 4.702], ) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], ) and SOD (0.820, [0.698; 0.964], ) were protective factors for the severity of diabetic microvascular complications.
CONCLUSION
Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Aged; Zinc; China; Oxidative Stress; Malondialdehyde; Superoxide Dismutase; Middle Aged; Blood Glucose; Risk Factors; Diabetic Angiopathies; Glycated Hemoglobin; Nitric Oxide; Antioxidants; Magnesium; Lipids; Trace Elements; Severity of Illness Index
PubMed: 38948168
DOI: 10.2147/CIA.S464615 -
Theranostics 2024Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer...
Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both and . Our findings provide an important theoretical basis for clinical prostate cancer treatment. Our and results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.
Topics: Male; Prostatic Neoplasms; Humans; Animals; Apoptosis; Histone Deacetylase Inhibitors; Cell Line, Tumor; Cell Cycle Checkpoints; cdc25 Phosphatases; Mice; Antineoplastic Agents; Cell Proliferation; Mice, Nude; Selenium; Xenograft Model Antitumor Assays; Prodrugs; Mice, Inbred BALB C
PubMed: 38948069
DOI: 10.7150/thno.92119 -
Frontiers in Immunology 2024The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.
Topics: Female; Humans; Bilirubin; Biomarkers; Oxidative Stress; Rheumatic Diseases; Male
PubMed: 38947324
DOI: 10.3389/fimmu.2024.1369284 -
Pulmonary Medicine 2024Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of...
BACKGROUND
Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of >1.
METHODS
The PubMed, Embase, Google Scholar, and CINAHL databases were searched using predetermined Boolean parameters. The systematic literature review was done per PRISMA guidelines. Retrospective studies, case series, case reports, and conference abstracts were included. The patients with reported pleural fluid analyses were pooled for fluid parameter data analysis.
RESULTS
Of 838 articles identified through the inclusion criteria and removing 105 duplicates, 732 articles were screened with abstracts, and 285 were screened for full article review. After this, 123 studies qualified for further detailed review, and of these, 115 were pooled for data analysis. The mean pleural fluid and serum bilirubin levels were 72 mg/dL and 61 mg/dL, respectively, with a mean pleural fluid-to-serum bilirubin ratio of 3.47. In most cases, the bilothorax was reported as a subacute or remote complication of hepatobiliary surgery or procedure, and traumatic injury to the chest or abdomen was the second most common cause. Tube thoracostomy was the main treatment modality (73.83%), followed by serial thoracentesis. Fifty-two patients (51.30%) had associated bronchopleural fistulas. The mortality was considerable, with 18/115 (15.65%) reported death. Most of the patients with mortality had advanced hepatobiliary cancer and were noted to die of complications not related to bilothorax.
CONCLUSION
Bilothorax should be suspected in patients presenting with pleural effusion following surgical manipulation of hepatobiliary structures or a traumatic injury to the chest. This review is registered with CRD42023438426.
Topics: Female; Humans; Bile; Bilirubin; Pleural Effusion; Thoracentesis; Thoracostomy; Aged
PubMed: 38947176
DOI: 10.1155/2024/3973056 -
Frontiers in Cellular and Infection... 2024In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary...
INTRODUCTION
In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles.
METHODS
Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators.
RESULTS
Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA.
CONCLUSION
The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.
Topics: Humans; Biliary Atresia; Gastrointestinal Microbiome; Cholestasis; Infant; Bile Acids and Salts; Male; Female; RNA, Ribosomal, 16S; Bilirubin; Bacteria; DNA, Ribosomal; Feces
PubMed: 38947125
DOI: 10.3389/fcimb.2024.1402329 -
The Yale Journal of Biology and Medicine Jun 2024Neuroinflammation, toxic protein aggregation, oxidative stress, and mitochondrial dysfunction are key pathways in neurodegenerative diseases like Alzheimer's disease... (Review)
Review
Neuroinflammation, toxic protein aggregation, oxidative stress, and mitochondrial dysfunction are key pathways in neurodegenerative diseases like Alzheimer's disease (AD). Targeting these mechanisms with antioxidants, anti-inflammatory compounds, and inhibitors of Aβ formation and aggregation is crucial for treatment. Marine algae are rich sources of bioactive compounds, including carbohydrates, phenolics, fatty acids, phycobiliproteins, carotenoids, fatty acids, and vitamins. In recent years, they have attracted interest from the pharmaceutical and nutraceutical industries due to their exceptional biological activities, which include anti-inflammation, antioxidant, anticancer, and anti-apoptosis properties. Multiple lines of evidence have unveiled the potential neuroprotective effects of these multifunctional algal compounds for application in treating and managing AD. This article will provide insight into the molecular mechanisms underlying the neuroprotective effects of bioactive compounds derived from algae based on and models of neuroinflammation and AD. We will also discuss their potential as disease-modifying and symptomatic treatment strategies for AD.
Topics: Alzheimer Disease; Humans; Microalgae; Seaweed; Animals; Neuroprotective Agents; Biological Products; Antioxidants
PubMed: 38947104
DOI: 10.59249/JNKB9714 -
International Journal of Nanomedicine 2024Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating...
PURPOSE
Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.
METHODS
First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).
RESULTS
TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.
CONCLUSION
TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.
Topics: Cerium; Animals; Mitochondria; Reactive Oxygen Species; Mice; Apoptosis; Hematopoiesis; Oxidative Stress; Cell Survival; Radiation-Protective Agents; Humans; Radiation Protection; Cell Line
PubMed: 38946882
DOI: 10.2147/IJN.S459607