Reduction Of Reactive Oxygen Species Research Articles

Downregulation of CPEB3 exacerbates cardiac injury by inhibiting cardiomyocyte adaptive metabolic reprogramming after myocardial infarction

Abstract Background Adaptive metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis in hypoxia plays a protective role in cardiomyocyte survival by reducing reactive oxygen species (ROS) and increasing ATP. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) influences protein translation by modulating 3' untranslated region (3'UTR) lengths through alternative polyadenylation (APA). However, the role of CPEB3 in cardiomyocyte after myocardial infarction (MI) remains unknown. Purpose This study aims to explore the function of CPEB3 in cardiomyocyte after MI. Methods Three GEO databases of mice MI (GSE110209, GSE114695 and GSE236374) were analyzed to identify CPEB3 dysregulation. Cardiomyocyte-specific CPEB3 knockout mice and CPEB3-knockdown neonatal mouse cardiomyocytes (NMCMs), RNA sequencing, flow cytometry, TUNEL staining, Seahorse, ROS and ATP measurements were used to investigate the impact of CPEB3. APA events analysis, RIP sequencing, CUT-TAG, 3’RACE, polysome profiling and dual luciferase report were performed to elucidate the mechanisms of CPEB3. Recombinant adeno-associated virus carrying cardiac troponin T promoter was used to evaluate the therapeutic efficacy of CPEB3 in mice with MI. Results CPEB3 expression was markedly reduced in the heart tissue after MI and in NMCMs after hypoxia. Cardiomyocyte-specific CPEB3 deletion aggravated cardiomyocyte apoptosis, enlarged infarct size, and exacerbated cardiac injury after MI. RNA sequencing revealed that CPEB3 deficiency predominantly inhibited glycolysis-related pathway, with a notable decrease in pyruvate dehydrogenase kinase 1 (PDK1) expression. In CPEB3-knockdown NMCMs, adaptive metabolic reprogramming from OXPHOS to glycolysis and ATP level were decreased in hypoxia, whereas ROS production was significantly enhanced, all of which resulted in apoptosis and were regulated by PDK1. Besides, PDK1 overexpression counteracted the effects of CPEB3 knockdown on metabolic pattern, ROS, ATP and apoptosis. Mechanistically, CPEB3 deficiency led to a shortened 3’UTR of the transcription factor forkhead box O3 (FOXO3), and a decline of FOXO3 protein level. CPEB3 protein was confirmed to directly bind to FOXO3 mRNA, and the translation efficiency of FOXO3 was decreased with CPEB3 knockdown. Furthermore, FOXO3 was found to activate the transcription of PDK1, and FOXO3 overexpression alleviated the decline of PDK1 and attenuated CPEB3 knockdown-induced apoptosis in hypoxia. Finally, cardiomyocyte-specific CPEB3 overexpression reduced cardiomyocyte apoptosis, suppressed myocardial fibrosis, and improved cardiac function by upregulating FOXO3 and PDK1 levels after MI. Conclusion CPEB3 could promote FOXO3 protein expression via APA of FOXO3 3’UTR, activate transcription of PDK1 and ultimately protect cardiomyocyte from apoptosis by restoring metabolic balance in hypoxia. CPEB3 may serve as a promising therapeutic target for cardiomyocyte apoptosis after MI.Schematic diagram

Chrysin alleviates salt stress in tomato by physiological, biochemical, and genetic mechanisms

Soil salinity greatly reduces agricultural productivity, especially in dry and semi-arid regions, by interfering with physiological and biochemical processes. This research aimed to determine whether Chrysin (Chr) can mitigate the negative effects of salinity on growth parameters, antioxidant enzyme activity, and gene expression in tomato (Solanum lycopersicum L.) plants. Experiments were conducted in a semi-controlled greenhouse, with plants subjected to varying concentrations of sodium chloride (NaCl) (0 and 100 mM) and Chr (0, 0.1, 0.5, and 1.0 mM). Results revealed that salinity stress significantly reduced plant height, leaf area, and chlorophyll content while increasing hydrogen peroxide (H2O2), malondialdehyde (MDA), and proline levels, indicating oxidative stress. Chr application alleviated these detrimental effects by enhancing the activity of antioxidant enzymes such as catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), thereby reducing reactive oxygen species (ROS) accumulation. Additionally, Chr treatments improved plant water status and mineral content under salt stress. Gene expression analysis showed that Chr positively regulated the transcription of salt tolerance-related genes, including HKT1-1, HKT1-2, and PIP1-2, which are associated with sodium ion transport and water balance. These findings suggest that Chr can be an effective biostimulant for enhancing salt tolerance in tomato plants by modulating physiological, biochemical, and genetic mechanisms. This study provides insights into Chr's potential as a sustainable solution for improving crop resilience to salinity in agricultural practices. Further research is recommended to optimize Chr concentrations for maximum efficacy.

Chlorella-enriched hydrogels protect against myocardial damage and reactive oxygen species production in an in vitro ischemia/reperfusion model using cardiac spheroids

Microalgae have emerged as promising photosynthetic microorganisms for biofabricating advanced tissue constructs, with improved oxygenation and reduced reactive oxygen species (ROS) production. However, their use in the engineering of human tissues has been limited due to their intrinsic growth requirements, which are not compatible with human cells. In this study, we first formulated alginate-gelatin (AlgGel) hydrogels with increasing densities ofChlorella vulgaris. Then, we characterised their mechanical properties and pore size. Finally, we evaluated their effects on cardiac spheroid (CS) pathophysiological response under control and ischemia/reperfusion (I/R) conditions. Our results showed that the addition ofChlorelladid not affect AlgGel mechanical properties, while the mean pore size significantly decreased by 35% in the presence of the 107cells ml-1microalgae density. Under normoxic conditions, the addition of 107Chlorellacells ml-1significantly reduced CS viability starting from 14 d in. No changes in pore size nor CS viability were measured for hydrogels containing 105and 106Chlorellacells ml-1. In our I/R model, allChlorella-enriched hydrogels reduced cardiac cell sensitivity to hypoxic conditions with a corresponding reduction in ROS production, as well as protected against I/R-induced reduction in cell viability. Altogether, our results support a promising use ofChlorella-enriched Alg-Gel hydrogels for cardiovascular tissue engineering.

Neuroprotective effect of empagliflozin against doxorubicin-induced chemobrain in rats: Interplay between SIRT-1/MuRF-1/PARP-1/NLRP3 signaling pathways and enhanced expression of miRNA-34a and LncRNA HOTAIR

Chemobrain, a challenging side effect of doxorubicin (DOX)-based chemotherapy, impairs cognitive abilities in cancer survivors. DOX triggers chemobrain via oxidative stress, leading to inflammation and apoptosis. Empagliflozin (EMPA), a sodium glucose co-transporter-2 inhibitor, demonstrated neuroprotective effects by reducing reactive oxygen species (ROS) and inflammation, but its protective mechanisms against DOX-induced chemobrain is not fully known. Thus, this study aimed to investigate EMPA’s neuroprotective effects on DOX-induced chemobrain in rats and to uncover the underlying protective mechanisms. Fifty male Wistar rats were divided into control, EMPA, DOX (2 mg/kg, IP, once/week for 4 weeks), and two treated groups (DOX+ EMPA 5 and 10 mg/kg/day, PO, for 4 weeks). Behavioral tests showed improved memory, motor performance, and reduced anxiety in EMPA-treated groups compared to DOX, with superior results at the higher dose. Histopathological analysis revealed increased intact neurons in the cortex and hippocampus in EMPA-treated groups, with 346.4 % increase in CA3 (p < 0.0001), 19.1 % in dentate gyrus (p = 0.0006), and 362.6 % in cortex (p < 0.0001) in the high-dose EMPA group. Biochemical investigations of the high-dose EMPA group revealed significant decreases in inflammatory and apoptotic markers (JNK/PARP-1/NLRP3/MuRF-1/FOXO-1), increased SIRT-1 protein expression by 389.9 % (p < 0.0001), and reduced miRNA-34a and LncRNA HOTAIR gene expression (50.4 % and 53.4 % respectively, p < 0.0001) relative to DOX group. Conclusively, EMPA demonstrated superior behavioral and histopathological outcomes particularly at higher dose, positioning it as a promising neuroprotective candidate against DOX-induced chemobrain, possibly through modulating SIRT-1, NF-κb, NLRP3, and oxidative stress pathways.

NIR-II Image-Guided Wound Healing in Hypoxic Diabetic Foot Ulcers: The Potential of Ergothioneine-Luteolin-Chitin Hydrogels.

Hypoxic diabetic foot ulcers (HDFUs) pose a challenging chronic condition characterized by oxidative stress damage, bacterial infection, and persistent inflammation. This study introduces a novel therapeutic approach combining ergothioneine (EGT), luteolin (LUT), and quaternized chitosan oxidized dextran (QCOD) to address these challenges and facilitate wound healing in hypoxic DFUs. In vitro, assessments have validated the biosafety, antioxidant, and antimicrobial properties of the ergothioneine-luteolin-chitin (QCOD@EGT-LUT) hydrogel. Furthermore, near-infrared II (NIR-II) fluorescence image-guided the application of QCOD@EGT-LUT hydrogel in simulated HDFUs. Mechanistically, QCOD@EGT-LUT hydrogel modulates the diabetic wound microenvironment by reducing reactive oxygen species (ROS). In vivo studies demonstrated increased expression of angiogenic factors mannose receptor (CD206)and latelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), coupled with decreased inflammatory factors tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6), thereby promoting diabetic wound healing through up-regulation of transforming growth factor β-1 (TGF-β1).

Platinum Nanozyme-Loaded Dissolving Microneedles Scavenge ROS and Promote Lineage Progression for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is a prevalent issue affecting the physical and mental health of individuals but with fewer current treatments. Platinum nanozymes (PtNZs) are known for their excellent ability to reduce and modulate the high oxidative stress environment in AGA pathology. And microneedles are used to overcome the skin barrier due to the poor permeability of PtNZs. Herein, dissolving microneedles loaded with PtNZs (Pt-MNs) are designed and successfully induced hair regeneration in the AGA model. Pt-MNs possessed adequate mechanical strength to breach the skin barrier for effective PtNZs delivery. In vivo, PtNZs first reduced reactive oxygen species (ROS) to oxygen, which recovered the AGA pathological environment. And the oxygen then increased oxidative phosphorylation, promoting the differentiation of hair follicle stem cells to achieve hair regeneration. The group treated with Pt-MNs with a dosing frequency of once every three days achieved faster hair growth than the daily application of the positive drug minoxidil. Further safety experiments showed that the application of Pt-MNs locally opened temporary and recoverable skin channels, with no retention of Pt in major organs, indicating high safety. In conclusion, this study indicated the potential of Pt-MNs as an effective method for treating AGA.

Reconfiguring the Escherichia coli Electron Transport Chain to Enhance trans-2-Decenoic Acid Production.

trans-2-Decenoic acid is a pivotal α,β-medium-chain unsaturated fatty acid that serves as an essential intermediary in the synthesis of 10-hydroxy-2-decenoic acid and various pharmaceutical compounds. Biosynthesis yield of trans-2-decenoic acid by decanoic acid has significantly improved in recent years; however, the oxidative stress of Escherichia coli at high fatty acid concentrations restricts the conversion rate. Here, we introduced a combination of rational design and metabolic rewiring of the E. coli electron transport chain (ETC) to improve trans-2-decenoic acid production. Overexpressing ubiquinone (UbQ) biosynthesis genes enhanced the expression of ETC complex III: UbQ to reduce reactive oxygen species (ROS) accumulation. Furthermore, applying rotenone to inhibit ETC complex I improved the electron transfer efficiency of complex II. The integration of Vitamin B5 and B2 into the fermentation process increased the activities of fatty acyl-CoA synthetase (MaMACS) and fatty acyl-CoA dehydrogenase (PpfadE). Finally, the constructed E. coli BL21(DE3)(ΔfadBJR/pCDFDuet-1-PpfadE-MaMACS/pRSFDuet-1-sumo-CtydiI-ubiI) strain exhibited a 51.50% decrease in ROS and a 93.33% enhancement in trans-2-decenoic acid yield, reaching 1.45 g/L after 66 h, which is the highest yield reported for flask fermentation. This study reports the feasibility of rewiring the ETC regulation and energy metabolism to improve α,β-UCA biosynthesis efficiency.

A novel synthetic compound, deferiprone–resveratrol hybrid (DFP-RVT), promotes hepatoprotective effects and ameliorates iron-induced oxidative stress in iron-overloaded β-thalassemic mice

A high amount of iron in β-thalassemia patients can lead to oxidative stress and organ dysfunction, especially liver, the main iron accumulated organ. Iron catabolism causes the generation of reactive oxygen species (ROS), triggering liver inflammation, fibrosis, and cirrhosis. Deferiprone-resveratrol hybrid (DFP-RVT) is chemically synthesized by combining deferiprone (DFP) and resveratrol (RVT) which shows an iron-chelating property along with antioxidant activity. This study explored the hepatoprotective effect of DFP-RVT in iron overloaded β-knockout (BKO) thalassemic mice. The results revealed that DFP-RVT treatment improved liver function in iron-overloaded BKO mice by reducing liver enzymes and increasing hepcidin levels compared to iron overload control mice. Both DFP alone and DFP-RVT treatment groups demonstrated iron chelation effects by decreasing liver iron content (LIC), iron profiles, and iron deposition in the liver. Moreover, DFP-RVT powerfully showed antioxidant properties by decreasing liver and plasma thiobarbituric acid reactive substances (TBARs) and increasing reduced glutathione (GSH) and superoxide dismutase (SOD). Interestingly, transforming growth factor β1 (TGFβ1), which can contribute to chronic liver disease through liver injury, inflammation, fibrosis, and cirrhosis, is highly expressed in iron-overloaded mice. However, both DFP and DFP-RVT treatment significantly reduced TGFβ1 levels compared to the iron-overloaded group. Therefore, DFP-RVT could be a potent hepatoprotective compound through the mobilization of iron, reduction of ROS, improvement of liver enzymes, and alleviation of liver damage, potentially relieving liver dysfunction in iron-overloaded BKO mice.

Buffy coat removal to mitigate reporting false normal G6PD phenotype results in patients undergoing rasburicase therapy for tumor lysis syndrome

Abstract Glucose-6-phosphate dehydrogenase (G6PD) is the primary source of NADPH in red blood cells (RBCs). NADPH reduces reactive oxygen species (ROS) thereby protecting RBCs from oxidative stress-mediated hemolytic anemia (HA). Individuals with partial or full G6PD deficiency are therefore susceptible to acute HA provoked by medications that generate high ROS loads in vivo, e.g., rasburicase. Rasburicase is an enzyme-based therapeutic used to degrade uric acid (UA) in patients with tumor lysis syndrome (TLS); however, catalysis of UA generates H2O2, a potent ROS, which poses a risk of HA in individuals who are deficient in G6PD activity. Screening G6PD activity prior to rasburicase administration is clinically indicated in ethnic groups with high rates of G6PD deficiency, although reports of HA in rasburicase-treated patients have been reported across low prevalence ethnic groups as well. TLS occurs most commonly during the treatment of highly proliferative neoplasms, such as leukemia and lymphoma. Since WBCs contain significant G6PD activity, an elevated WBC count in these patients can cause the false assurance of low HA risk due to a falsely normal G6PD activity. We sought to establish and evaluate a novel method to mitigate WBC contamination of G6PD measurements in patients undergoing rasburicase therapy. In this study, we first developed and validated an innovative method (“piercing method”) to minimize the interference of WBCs in G6PD measurements. The piercing method demonstrated acceptable accuracy (slope: 1.008; bias: -6.22%) and precision (1.4% CV between 9.9 to 20.7 U/g Hb) and was effective at eliminating a broad range of WBC types and concentrations from whole blood samples (N = 85, tested range = 0.31 – 413.05 K/μL, 93% reduction in WBCs). We compared G6PD activity in rasburicase-treated patients (N = 39) with varying WBC counts before and after buffy coat removal using the piercing method. Average percent change in G6PD activity (post-pierce – pre-pierce) between patients with and without elevated WBCs was substantial (45% versus 12%). In comparing G6PD activity in patients before and after the initiation of rasburicase therapy, there is no evidence that in vivo-generated ROS from rasburicase affect G6PD measurement in vitro in an assay that relies on monitoring absorbance of NADPH (22.2 U/g Hb versus 22.9 U/g Hb, p=0.721). Results demonstrate how WBCs increase risk for false elevation in G6PD activity in patients being considered for rasburicase therapy. At greatest risk are patients with partial G6PD deficiency, e.g., heterozygous females, where G6PD from WBCs could mask deficiency. Literature describing testing of G6PD in specimens with elevated WBCs is lacking. This study shows that the piercing method provides accurate G6PD results in samples with elevated WBCs from patients at risk of TLS, who might develop HA after starting rasburicase therapy.

Using rhamnolipid as a promoter to improve the production of germacrene A by Yarrowia lipolytica

AbstractSignificant progress has recently been made in the biosynthesis of germacrene A using microbial cell factories. Germacrene A is a crucial precursor for the synthesis of anti‐cancer active compounds. However, its hydrophobic characteristics lead to its aggregation in cell membranes and cause severe cytotoxicity. In the present study, we found that rhamnolipids (RLs), as toxicity antidotes, could promote the production of germacrene A. An optimal RLs concentration of 1.25 g L−1 resulted in an increase of over 30% in the germacrene A titer at both shake flask and bioreactor scales. Mechanistic analysis showed that the addition of RLs could dramatically reduce aqueous‐phase surface tension and cell surface hydrophobicity (CSH), and increase the cell membrane permeability. This, in turn, promoted an efficient transfer of germacrene A from cell membrane to extraction phases. The addition of RLs also increased the adenosine triphosphate (ATP) concentration and the nicotinamide adenine dinucleotide (NAD+/NADH) ratio, while reducing reactive oxygen species (ROS) levels. Correspondingly, gene transcripts for key enzymes associated with germacrene A biosynthesis, the respiratory chain, and ROS scavenging were upregulated significantly. This study provides an effective RLs‐regulated fermentation method for the biosynthesis of hydrophobic natural products.

Selenomethionine Mitigates Effects of Nocardia cyriacigeorgica-Induced Inflammation, Oxidative Stress, and Apoptosis in Bovine Mammary Epithelial Cells

Nocardia cyriacigeorgica causes bovine mastitis, reduces milk quantity and quality, and is often resistant to antimicrobials. Selenomethionine (SeMet) is a form of selenium, which reduces reactive oxygen species (ROS)-mediated apoptosis and intramammary infections. However, the protective effects of SeMet on N. cyriacigeorgica-infected bovine mammary epithelial cells (bMECs) are unclear. The objective of this study was to evaluate whether SeMet mitigated N. cyriacigeorgica-induced inflammatory injury, oxidative damage and apoptosis in bMECs. Cells were cultured with or without being pretreated with 40 µM of SeMet for 12 h, then challenged with N. cyriacigeorgica (multiplicity of infection = 5:1) for 6 h. Although N. cyriacigeorgica was resistant to lincomycin, erythromycin, enrofloxacin, penicillin, amoxicillin, cephalonium, cephalexin, and ceftriaxone, 40 μM SeMet increased cell viability and inhibited lactate dehydrogenase release in infected bMECs. Furthermore, N. cyriacigeorgica significantly induced mRNA production and protein expression of TNF-α, IL-1β, IL-6, and IL-8 at 6 h. Cell membrane rupture, cristae degeneration and mitochondria swelling were evident with transmission electron microscopy. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities were down-regulated after 3, 6, or 12 h, whereas malondialdehyde (MDA) and ROS contents were significantly upregulated, with cell damage and apoptosis rapidly evident (the latter increased significantly in a time-dependent manner). In contrast, bMECs pretreated with 40 μM SeMet before infection, SOD, and GSH-px activities were upregulated (p &lt; 0.05); MDA and ROS concentrations were downregulated (p &lt; 0.05), and apoptosis was reduced (p &lt; 0.05). In conclusion, 40 μM SeMet alleviated inflammation, oxidative stress and apoptosis induced by N. cyriacigeorgica in bMECs cultured in vitro.

Protective Effects of Astaxanthin against Oxidative Stress: Attenuation of TNF-α-Induced Oxidative Damage in SW480 Cells and Azoxymethane/Dextran Sulfate Sodium-Induced Colitis-Associated Cancer in C57BL/6 Mice.

In this study, we investigated the protective effects of astaxanthin (AST) against oxidative stress induced by the combination of azoxymethane (AOM) and dextran sulfate sodium (DSS) in colitis-associated cancer (CAC) and TNF-α-induced human colorectal cancer cells (SW480), as well as the underlying mechanism. In vitro experiments revealed that astaxanthin reduced reactive oxygen species (ROS) generation and inhibited the expression of Phosphorylated JNK (P-JNK), Phosphorylated ERK (P-ERK), Phosphorylated p65 (P-p65), and the NF-κB downstream protein cyclooxygenase-2 (COX-2). In vivo experiments showed that astaxanthin ameliorated AOM/DSS-induced weight loss, shortened the colon length, and caused histomorphological changes. In addition, astaxanthin suppressed cellular inflammation by modulating the MAPK and NF-κB pathways and inhibiting the expression of the proinflammatory cytokines IL-6, IL-1β, and TNF-α. In conclusion, astaxanthin attenuates cellular inflammation and CAC through its antioxidant effects.

Acid-triggered rattan ball-like β-glucan carrier embedding doxorubicin to synergistically alleviate precancerous lesions of gastric cancer via p53 and PI3K pathways

The early intervention of precancerous lesions of gastric cancer (PLGC) is crucial for improving the survival of patients with gastric cancer. Traditional pharmaceuticals for the treatment of PLGC are limited by side effects, thus developing innovative drug carrier that are more efficient but without the undesirable side effects is required. Here, we proposed an acid-triggered mushroom-derived β-glucan carrier embedding doxorubicin (DOX) to circumvent drug cytotoxicity and synergistically alleviate PLGC based on the controlled conformational transformation. The triple helix β-glucan extracted from Dictyophora rubrovolvata (DRP) loaded doxorubicin driven by pH and DMSO regulation, forming two rattan ball-like nanoparticles (DRP-DOX(pH) and DRP-DOX(DMSO)) via its collapse and recombination of triple-helix conformation. The findings revealed that DRP-DOXs achieved acid-triggerable and sustained drug delivery with an average particle size of 500 nm and 550 nm. In vitro evaluation of GES-1 cells showed DRP-DOXs reduced reactive oxygen species (ROS) production and altered mitochondrial membrane potential. Compared to DRP-DOX(DMSO) and DRP, DRP-DOX(pH) could more effectively downregulate cellular oxidative stress and inflammation to eventually alleviate PLGC, by regulating the p53 and PI3K pathways to mitigate gastric mucosa damage. Consequently, the nature-derived β-glucan delivery nanovesicle holds great promising applications in reducing drug toxicity and suppressing the development of PLGC.

Multifaceted Impact of SGLT2 Inhibitors in Heart Failure Patients: Exploring Diverse Mechanisms of Action.

Heart failure (HF) is a growing concern due to the aging population and increasing prevalence of comorbidities. Despite advances in treatment, HF remains a significant burden, necessitating novel therapeutic approaches. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have emerged as a promising treatment option, demonstrating benefits across the entire spectrum of HF, regardless of left ventricular ejection fraction (LVEF). This review explores the multifaceted mechanisms through which SGLT2is exert cardioprotective effects, including modulation of energy metabolism, reduction of oxidative stress, attenuation of inflammation, and promotion of autophagy. SGLT2is shift myocardial energy substrate utilization from carbohydrates to more efficient fatty acids and ketone bodies, enhancing mitochondrial function and reducing insulin resistance. These inhibitors also mitigate oxidative stress by improving mitochondrial biogenesis, reducing reactive oxygen species (ROS) production, and regulating calcium-signaling pathways. Inflammation, a key driver of HF progression, is alleviated through the suppression of proinflammatory cytokines and modulation of immune cell activity. Additionally, SGLT2is promote autophagy, facilitating the clearance of damaged cellular components and preserving myocardial structure and function. Beyond their glucose-lowering effects, SGLT2is provide significant benefits in patients with chronic kidney disease (CKD) and HF, reducing the progression of CKD and improving overall survival. The pleiotropic actions of SGLT2is highlight their potential as a cornerstone in HF management. Further research is needed to fully elucidate their mechanisms and optimize their use in clinical practice.

Hyaluronic acid-functionalized carboxymethyl dextran-coated melatonin nanoconjugates for targeted etoposide delivery in metastatic colon cancer: Extensive in-vitro investigation in HCT116 cell lines, antimicrobial efficacy, and anti-angiogenic potential in chick chorioallantoic membrane (CAM) assay

Managing advanced colon cancer is challenging, requiring targeted therapies. This study presents a novel nanoconjugate system, HA-CMD@ETP-MLT-NCs, designed to deliver etoposide (ETP) specifically to colon cancer cells. The system consists of Hyaluronic Acid (HA)-Functionalized Carboxymethyl Dextran (CMD) coated with Melatonin (MLT). The nanoconjugates showed good stability, with a zeta potential of −29.90 mV and a particle size of 199.1 nm. They achieved an 80.3 % yield and a high drug entrapment efficiency of 93.4 %. In vitro release studies demonstrated pH-dependent drug release, with 73.4 % released at pH 5.5 (tumour-like environment) and 42.6 % at pH 7.4 (normal tissue) over 24 h. The nanoconjugates improved cellular uptake, induced apoptosis, and reduced reactive oxygen species (ROS) in HCT116 colon cancer cells. Flow cytometry showed a significant decrease in ROS levels, and lipid peroxidation inhibition increased to 56.67 %. These findings suggest that HA-CMD@ETP-MLT-NCs enhance etoposide delivery and reduce side effects. Further in vivo studies and clinical trials are needed to confirm its therapeutic potential.

Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications.

Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor responsible for cytoprotection, plays a crucial role in regulating the expression of numerous antioxidant genes, thereby reducing reactive oxygen species (ROS) levels and safeguarding cells against oxidative stress. Extensive research has demonstrated the involvement of Nrf2 in various diseases, prompting the exploration of Nrf2 activation as a potential therapeutic approach for a variety of diseases. Consequently, there has been a surge of interest in investigating the Nrf2 signaling pathway and developing compounds that can modulate its activity. Isoliquiritigenin (ISL) (PubChem CID:638278) exhibits a diverse range of pharmacological activities, including antioxidant, anticancer, and anti-tumor properties. Notably, its robust antioxidant activity has garnered significant attention. Furthermore, ISL has been found to possess therapeutic effects on various diseases, such as diabetes, cardiovascular diseases, kidney diseases, and cancer, through the activation of the Nrf2 pathway. This review aims to evaluate the potential of ISL in modulating the Nrf2 signaling pathway and summarize the role of ISL in diverse diseases prevention and treatment through modulating the Nrf2 signaling pathway.

Comparative Physiological, Biochemical, and Leaf Proteome Responses of Contrasting Wheat Varieties to Drought Stress.

Drought stress severely affects crop productivity and threatens food security. As current trends of global warming are predicted to exacerbate droughts, developing drought-resilient crops becomes urgent. Here, we used the drought-tolerant (BW35695) and drought-sensitive (BW4074) wheat varieties to investigate the physiological, biochemical, and leaf proteome responses underpinning drought tolerance. In response to drought, the tolerant variety had higher osmolyte accumulation and maintained higher leaf water content than the sensitive variety. BW35695 also had an enhanced antioxidant enzyme capacity and reduced reactive oxygen species (ROS), resulting in diminished membrane lipid damage, as reflected by malondialdehyde content. Proteomic analysis revealed that drought-induced differential expression of proteins involved in diverse biological processes in both wheat varieties, including primary and secondary metabolism, protein synthesis/folding/degradation, defense/ROS detoxification, energy, transcription, and cell structure. Notably, photosynthesis emerged as the most enriched biochemical process targeted for suppression in the drought-tolerant BW35695 wheat, but not in drought-sensitive BW4074, possibly as a survival strategy for averting cell damage inflicted by photosynthesis-derived ROS. Additionally, protein synthesis-related proteins were highly upregulated in BW35695, presumably to drive cell-wide stress-adaptive responses. The protein network identified here will be useful in further studies to understand the molecular basis for divergent drought response phenotypes in crops.

Exploring the Therapeutic Potential of Green Tea (Camellia sinensis L.) in Anti-Aging: A Comprehensive Review of Mechanisms and Findings.

Green tea (GT) is rich in Phyto-active compounds such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), catechin, and tannic acid, which exhibit synergistic effects when combined. Preclinical studies demonstrate that GT and its compounds can reduce reactive oxygen species (ROS), enhance antioxidant capacity, and alleviate aging-related issues such as memory impairments, cognitive decline, and shortened lifespan. Clinical trials corroborate the efficacy of topical GT formulations in improving skin tone, texture, and elasticity and reducing wrinkles. The present manuscript summarizes the recent update on the anti-aging potential of GT and its possible mechanisms. The literature survey suggested that GT consumption is linked to improved cognition, reduced depression levels, and activation of pathways in model organisms like C. elegans. Additionally, tea polyphenols enhance fibroblast mitophagy, boost hippocampal synaptic plasticity in rodents, and mitigate age-related cognitive decline. Moreover, EGCG exhibits anti-aging properties by reducing TNF-induced MMP-1 expression, suppressing ERK signaling, and inhibiting MEK and Src phosphorylation in human dermal fibroblasts. In the context of skin permeation and deposition, optimized transpersonal formulation (TF) incorporating EGCG and hyaluronic acid (HA) demonstrated significantly increased skin permeation and deposition of EGCG compared to plain EGCG. Furthermore, EGCG protects cardiomyocytes via the PPARγ pathway and combats age-related muscle loss through miRNA-486-5p regulation, AKT activation, and FoxO1a-mediated expression of MuRF1 and Atrogin-1. In conclusion, the regular consumption of GT holds promise for promoting physical and mental health, delaying brain and skin aging, and improving overall health by enhancing total antioxidant capacity.

Mechanistic studies on the alleviation of lipid accumulation and oxidative stress by Majia pomelo seed oil

In this study, hot-pressed Majia pomelo seed oil (MPSO), which has high oxidative stability and antioxidant capacity, was used to study the effects and potential mechanisms of lipid accumulation and oxidative stress. The results indicated that the low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) levels in HepG2 cells were lowest when the MPSO concentration was 0.5 mg/mL. At this concentration, MPSO could alleviate oleic acid (OA)-induced lipid accumulation, reduce intracellular lipid level, and decrease lipid and cholesterol synthesis by increasing AMPK phosphorylation and down-regulating the expression levels of genes and proteins of ACC, SREBP-1c, PPAR-γ, and FAS. Meanwhile, MPSO can reduce reactive oxygen species (ROS) and malondialdehyde (MDA) content and enhance superoxide dismutase (SOD) content in HepG2 cells by down-regulating the expression levels of Nrf2, γ-GCS, and HO-1 genes and proteins, thus acting as an anti-oxidative stress. In addition, molecular docking results indicated that the active ingredients of MPSO could effectively bind AMPK protein and Keap1 protein, which further demonstrated that MPSO could alleviate lipid accumulation and oxidative stress.

Integrated transcriptomic and proteomic analysis revealed the regulatory role of 5-azacytidine in kenaf salt stress alleviation

Salinity stress limits agricultural production. The DNA methyltransferase inhibitor, 5-azacitidine (5-azaC), plays a role in plant abiotic stress regulation, but its molecular basis in mediating salinity tolerance in kenaf remains unclear. To investigate the effects on 5-azaC on alleviating salt stress, kenaf seedlings were pre-treated with 0, 50, 100, 150, and 200 μM 5-azaC and then exposed to 150 mM NaCl in a nutrient solution. Physiological, transcriptomic, and proteomic analyses were conducted on the root system to understand the regulatory mechanism of 5-azaC (comparing 5-azaC150 and control group 5-azaC0) under salt stress. The results indicated that 5-azaC significantly mitigated salt stress in kenaf by activating the antioxidant system, reducing reactive oxygen species (ROS), and increasing starch, soluble sugars, and adenosine triphosphate (ATP) content. A total of 14,348 differentially expressed genes (DEGs) and 313 differentially abundant proteins (DAPs) were identified. Combined proteomic and transcriptomic analysis revealed 27 DEGs/DAPs, with jointly up-regulated proteins (genes) including HcTHI1, HcBGLU11, and HcCBL1, and jointly down-regulated proteins (genes) including HcGAPDH, HcSS, and HcPP2C52. Overexpression and virus-induced gene silencing (VIGS) of HcPP2C52 demonstrated its role as a negative regulator of salt tolerance. These findings provide insights into the regulatory role of 5-azaC in plant responses to abiotic stresses. SignificanceThe specific molecular mechanism by which 5-azaC affects gene expression and protein activity of kenaf has been revealed, leading to enhanced salt tolerance.