Reactive Oxygen Species Scavenger Research Articles

Thiostrepton as a Potential Therapeutic Agent for Hepatocellular Carcinoma.

Due to limited drug efficacy and drug resistance, it is urgent to explore effective anti-liver cancer drugs. Repurposing drugs is an efficient strategy, with advantages including reduced costs, shortened development cycles, and assured safety. In this study, we adopted a synergistic approach combining computational and experimental methods and identified the antibacterial drug thiostrepton (TST) as a candidate for an anti-liver cancer drug. Although the anti-tumor capabilities of TST have been reported, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unclear. TST was found here to inhibit the proliferation of HCC cells effectively, arresting the cell cycle and inducing cell apoptosis, as well as suppressing the cell migration. Further, our findings revealed that TST induced mitochondrial impairment, which was demonstrated by destroyed mitochondrial structures, reduced mitochondria, and decreased mitochondrial membrane potential (MMP). TST caused the production of reactive oxygen species (ROS), and the mitochondrial impairment and proliferation inhibition of HCC cells were completely restored by the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we discovered that TST induced mitophagy, and autophagy inhibition effectively promoted the anti-cancer effects of TST on HCC cells. In conclusion, our study suggests TST as a promising candidate for the treatment of liver cancers, and these findings provide theoretical support for the further development and potential application of TST in clinical liver cancer therapy.

Highly aligned electroactive ultrafine fibers promote the differentiation of mesenchymal stem cells into Schwann-like cells for nerve regeneration

This study investigates the efficacy of a novel tissue-engineered scaffold for nerve repair and functional reconstruction following injury. Utilizing stable jet electrospinning, we fabricated aligned ultrafine fibers from dopamine and poly(L-lactic acid) (PLLA), further developing a biomimetic, oriented, and electroactive scaffold comprising poly(pyrrole) (PPy), polydopamine (PDA), and PLLA through dual in situ polymerizations. The scaffold demonstrated enhanced cell adhesion and reactive oxygen species (ROS) scavenging capabilities and promoted the differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells, essential for nerve regeneration. In vivo assessments revealed significant peripheral nerve regeneration in 10 mm sciatic nerve defects in rats, with observations made 12 weeks post-transplantation. This included facilitated myelination and increased muscle density on the injured side, leading to improved motor function recovery. Our results suggest that the aligned PPy/PDA/PLLA fibrous scaffold offers a promising approach for promoting the differentiation of MSCs into Schwann-like cells conducive to nerve regeneration and represents a significant advancement in nerve repair technologies. This study provides a foundational basis for future research into tissue-engineered solutions for nerve damage, potentially impacting clinical strategies for nerve reconstruction.

Exploring the potential of nanoparticles-based polydopamine for effective treatment of refractory keratitis: Mild photothermal loop therapy

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice.

Two-step emulsification for the fabrication of homogeneous PCL microspheres encapsulating geniposidic acid with antioxidant properties

The mortality rate of neurological disorders is increasing globally, and natural antioxidant geniposidic acid (GPA) holds great potential in the treatment of neuronal oxidative damage. Nevertheless, its inherent instability constrains its pragmatic utilization. Herein, we introduced a drug delivery system capable of protecting unstable natural active compounds from degradation. Among the various methods for preparing drug-loaded microspheres, the emulsification-solvent evaporation technique is one of the most commonly employed due to its efficiency and simplicity. Nevertheless, this method results in microspheres with heterogeneous particle sizes. To address this limitation, we developed a two-step emulsification method involving stirring and homogenization. Using the biocompatible, synthetic, biodegradable polymer polycaprolactone (PCL) as the drug delivery carrier, we prepared GPA-loaded PCL microspheres via the two-step emulsification method. The results demonstrated that the microspheres possessed uniform particle size (polydispersity index = 0.12), excellent drug loading capacity (∼4.86%), sustained drug release profiles (∼68.55% in 264 h), and biocompatibility (cell viability >85%). The in vitro tests showed that the microspheres exerted antioxidant effects by scavenging reactive oxygen species (ROS) induced by oxidative stress, thereby protecting neuronal cells from oxidative damage. This work presents a promising new approach for the treatment of neuronal oxidative damage.

Enhancing Growth in Vigna radiata through the Inhibition of Charcoal Rot Disease: A Strategic Approach Using Plant Growth-Promoting Rhizobacteria.

Macrophomina phaseolina is a vital seed and soil-borne phytopathogen responsible for substantial crop yield losses. Although various methods exist for managing soil-borne pathogens, such as agronomic practices, chemical treatments, and varietal tolerance, biological control utilizing plant growth-promoting rhizobacteria (PGPR) or their secondary metabolites presents promising avenues. In this study, a screening of 150 isolates from the rhizosphere of Vigna radiata L. was conducted to identify strains capable of promoting host growth and controlling charcoal rot disease. Among the tested isolates, only 15 strains demonstrated the ability to produce plant growth-related metabolites, including indole acetic acid, hydrogen cyanide, ammonia, and lytic enzymes, and solubilize inorganic phosphate. Subsequently, these potent strains were evaluated for their antifungal activity against Macrophomina phaseolina in vitro. Three strains, namely MRP-7 (58% growth inhibition), MRP-12 (55% growth inhibition), and MRP-8 (44% growth inhibition), exhibited the highest percent growth inhibition (PGI.). Furthermore, a pot experiment demonstrated that the selected strains acted as effective growth promoters and ROS (reactive oxygen species) scavengers, and served as potential biocontrol agents, significantly reducing the incidence of charcoal rot disease and improving various agronomic attributes of the host plant. These findings highlight the potential of these strains to be utilized as biofertilizers and biocontrol agents for sustainable agricultural practices.

EP4 receptor agonist CAY10598 upregulates ROS-dependent Hsp90 cleavage in colorectal cancer cells

Prostaglandin E2 (PGE2) interacts with four specific G protein-coupled receptors, namely EP1, EP2, EP3, and EP4, playing a pivotal role in determining the fate of cells. Our previous findings highlighted that stimulating the EP4 receptor with its agonist, CAY10598, triggers apoptosis in colon cancer HCT116 cells via the production of reactive oxygen species (ROS). This process also reduces the phosphorylation of the oncogenic protein JAK2 and leads to its degradation in these cells. In this study, our goal was to explore the pathways through which CAY10598 leads to JAK2 degradation. We focused on Hsp90, a heat shock protein family member known for its role as a molecular chaperone maintaining the stability of several key proteins including EGFR, MET, Akt, and JAK2. Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS. Furthermore, we observed that CAY10598 cleaves both α and β isoforms of Hsp90, the process inhibited by NAC. Inhibition of EP4 with the antagonist GW627368x not only prevented the degradation of Hsp90 client proteins but also the cleavage of Hsp90 itself in CAY10598-treated HCT116 cells. Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on “bio-orthogonal chemistry”, combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway.

Glioma is a refractory malignant tumor with a powerful capacity for invasiveness and a poor prognosis. This study aims to investigate the role and mechanism of tubulin beta class IVA (TUBB4A) in glioma progression. The differential expression of TUBB4A in humans was obtained from databases and analyzed. Glioma cells U251-MG and U87-MG were intervened by pcDNA3.1(+) and TUBB4A overexpression plasmid. MTT, CCK8, LDH, wound healing, transwell, and western blotting were used to explore whether TUBB4A participates in the development of glioma. Reactive oxygen species (ROS) were detected by the DCFH-DA probe. Mitochondrial membrane potential (MMP) was examined by JC-1. It was found thatTUBB4A expression level correlated with tumor grade, IDH1 status,1p/19q status, and poor survival in glioma patients. In addition, TUBB4A overexpression inhibited the proliferation, migration, and invasion of U251-MG and U87-MG, while increasing the degree of apoptosis. Notably, TUBB4A overexpression promotes ROS generation and MMP depolarization, and induces mitophagy through the PINK1/Parkin pathway. Interestingly, mitochondria-targeted ROS scavenger reversed the effect of TUBB4A overexpression on PINK1/Parkin expression and mitophagy, whereas mitophagy inhibitor did not affect ROS production. And the effect of TUBB4A overexpression on mitophagy and glioma progression was consistent with that of PINK1/Parkin agonist. In conclusion,TUBB4A is a molecular marker for predicting the prognosis of glioma patients and an effective target for inhibiting glioma progression by regulating ROS-PINK1/Parkin-mitophagy pathway.

Apple vacuolar sugar transporters regulated by MdDREB2A enhance drought resistance by promoting accumulation of soluble sugars and activating ABA signaling

Abstract Soluble sugars are not only an important contributor to fruit quality, but also serve as the osmotic regulators in response to abiotic stresses. Early drought stress promotes sugar accumulation, while specific sugar transporters govern the cellular distribution of the sugars. Here, we show that apple plantlets accumulate soluble sugars in leaf tissues under drought stress. Transcriptional profiling of stressed and control plantlets revealed differential expression of several plasma membrane- or vacuolar membrane-localized sugar transporter genes. Among these, four previously identified vacuolar sugar transporter (VST) genes (MdERDL6–1, MdERDL6–2, MdTST1 and MdTST2) showed higher expression under drought, suggesting their roles in response to drought stress. Promoter cis-elements analyses, yeast one-hybrid and dual-luciferase tests confirmed that the drought-induced transcription factor MdDREB2A could promote the expression of MdERDL6–1/−2 and MdTST1/2 by binding to their promoter regions. Moreover, overexpressing of each of these four MdVSTs alone in transgenic apple or Arabidopsis plants accumulated more soluble sugars and abscisic acid, and enhanced drought resistance. Furthermore, apple plants overexpressing MdERDL6–1 also showed reduced water potential, facilitated stomatal closure and reactive oxygen species scavenging under drought condition compared to control plants. Overall, our results suggest a potential strategy to enhance drought resistance and sugar accumulation in fruits through manipulating the genes involved in vacuolar sugar transport.

Copper tannate nanosheets-embedded multifunctional coating for antifouling and photothermal bactericidal applications

Implant-associated infections (IAIs), triggered by pathogenic bacteria, are a leading cause of implant failure. The design of functionalized coatings on biomedical materials is crucial to address IAIs. Herein, a multifunctional coating with good antifouling effect and antibacterial photothermal therapy (aPTT) performance was developed. The copper tannate nanosheets (CuTA NSs) were formed via coordination bonding of Cu2+ ions and tannic acid (TA). The CuTA NSs were then integrated into the TA and poly(ethylene glycol) (PEG) network to form the TCP coating for deposition on the titanium (Ti) substrates via surface adhesion of TA and gravitational effect. The resulting Ti-TCP substrate exhibited good antifouling property, reactive oxygen species (ROS) scavenging capability and cytocompatibility. The TCP coating exhibited antifouling efficacy in conjunction with aPTT, curtailing the surface adhesion and biofilm formation of pathogens, such as Staphylococcus aureus and Escherichia coli. Notably, the Ti-TCP substrate also exhibited the ability to prevent bacterial infection in vivo in a subcutaneous implantation model. The present work demonstrated a promising approach in designing high-performance antifouling and photothermal bactericidal coatings to combat IAIs.

Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

PM2.5 Induces Pyroptosis via Activation of the ROS/NF-κB Signaling Pathway in Bronchial Epithelial Cells.

Background and Objectives: Fine particulate matter, PM2.5, is becoming a major threat to human health, particularly in terms of respiratory diseases. Pyroptosis is a recently discovered and distinct form of cell death, characterized by pore formation in the cell membrane and secretions of proinflammatory cytokines. There has been little research on the effect of PM2.5 on pyroptosis, especially in airway epithelium. We investigated whether PM2.5-related oxidative stress induces pyroptosis in bronchial epithelial cells and defined the underlying mechanisms. Materials and Methods: After exposure of a BEAS-2B cell line to PM2.5 concentration of 20 µg/mL, reactive oxygen species (ROS) levels, parameters related to pyroptosis, and NF-κB signaling were measured by Western blotting, immunofluorescence, and ELISA (Enzyme-linked immunosorbent assay). Results: PM2.5 induced pyroptotic cell death, accompanied by LDH (Lactate dehydrogenase) release and increased uptake of propidium iodide in a dose-dependent manner. PM2.5 activated the NLRP3-casp1-gasdermin D pathway, with resulting secretions of the proinflammatory cytokines IL-1β and IL-18. The pyroptosis activated by PM2.5 was alleviated significantly by NLRP3 inhibitor. In PM2.5-exposed BEAS-2B cells, levels of intracellular ROS and NF-κB p65 increased. ROS scavenger inhibited the expression of the NLRP3 inflammasome, and the NF-κB inhibitor attenuated pyroptotic cell death triggered by PM2.5 exposure, indicating that the ROS/NF-κB pathway is involved in PM2.5-induced pyroptosis. Conclusions: These findings show that PM2.5 exposure can cause cell injury by NLRP3-inflammasome-mediated pyroptosis by upregulating the ROS/NF-κB pathway in airway epithelium.

Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy

Telethonin/titin-cap (TCAP) encodes a Z-disc protein that plays important roles in sarcomere/T-tubule interactions, stretch-sensing and signaling. Mutations in TCAP are associated with muscular dystrophy and cardiomyopathy; however, the complete etiology and its roles in myocardial infarction and regeneration are not fully understood. Here, we generated tcap gene knockout zebrafish with CRISPR/Cas9 technology and observed muscular dystrophy-like phenotypes and abnormal mitochondria in skeletal muscles. The stretch-sensing ability was inhibited in tcap‐/‐ mutants. Moreover, Tcap deficiency led to alterations in cardiac morphology and function as well as increases in reactive oxygen species (ROS) and mitophagy. In addition, the cardiac regeneration and cardiomyocyte proliferation ability of tcap‐/‐ mutants were impaired, but these impairments could be rescued by supplementation with ROS scavengers or autophagy inhibitors. Overall, our study demonstrates the essential roles of Tcap in striated muscle function and heart regeneration. Additionally, elevations in ROS and autophagy may account for the phenotypes resulting from Tcap deficiency and could serve as novel therapeutic targets for muscular dystrophy and cardiomyopathy.

Thermo-sensitive poly(amino acid) hydrogel mediates cytoprotection through an antioxidant mechanism

Oxidative stress, characterized by the excessive accumulation of reactive oxygen species (ROS), is linked to various pathological conditions, including myocardial infarction, cancer, and neurodegenerative diseases. Addressing ROS-induced cell damage has become a critical focus of biomedical research. In this study, a thermo-sensitive poly(amino acid) hydrogel, composed of poly(ethylene glycol)-block-poly(L-methionine), was prepared for cytoprotection through ROS scavenging. The sol-to-gel transition mechanism of the hydrogel was elucidated, and its potent antioxidant properties and cell protective effects were validated using hydrogen peroxide (H2O2)-induced oxidative stress and oxygen-glucose deprivation (OGD) models. The hydrogel significantly mitigated H2O2-induced damage in L929 cells, doubling their survival rate. Additionally, it scavenged approximately 35.8% of the ROS during OGD, reducing mitochondrial oxidative damage and resulting in a 29.4% decrease in apoptotic cell numbers. These findings underscore the potential biomedical applications of thermo-sensitive poly(amino acid) hydrogels, particularly in treating oxidative stress-related cell damage.

Ultraviolet-induced melanisation in lichens: physiological traits and transcriptome profile.

Lichens are important components of high-latitude boreal and Arctic habitats. While stress tolerant, they are among the most sensitive ecosystem components to climate change, in particular, an increase in ultraviolet light (UV) arising from polar ozone depletion and deforestation. This study is the first to explore the effects of UV-B on gene expression in lichens to predict metabolic pathways involved in tolerance. Using transcriptome profiling and bioinformatic analyses, here we studied the effects of UV-B on gene expression in lichens using Lobaria pulmonaria (L.) Hoff. as a model species. UV-B exposure causes significant browning of the upper cortex of the thallus, which correlates to an increased expression of biosynthetic gene clusters involved in the synthesis of eu- and allomelanins and melanin precursors. Based on transcriptome analyses, we suggest that the biosynthesis of melanins and other secondary metabolites, such as naphthalene derivates, tropolones, anthraquinones, and xanthones, is a trade-off that lichens pay to protect essential metabolic processes such as photosynthesis and respiration. Expression profiles of general stress-associated genes, in particular, related to reactive oxygen species scavenging, protection of proteins, and DNA repair, clearly indicate that the mycobiont is the more UV-B-responsive and susceptible partner in lichen symbiosis. Our findings demonstrate that UV-B stress activates an intricate gene network involved in tolerance mechanisms of lichen symbionts. Knowledge obtained here may enable the prediction of likely effects on lichen biodiversity caused by climate change and pollution.

Brassinosteroid improves resistance to phosphorus deficiency stress through regulating nutrient balance and reactive oxygen species scavenging in potato

Brassinosteroid (BR) plays a crucial role in plant growth, development and response to abiotic stress. However, the mechanism by which BR regulates the response of potato plants to phosphorus deficiency stress is still largely unknown. In this work, the effects of BR on the growth of potato plants under phosphorus deficient condition were investigated. Exogenous BR application mitigated the growth inhibition caused by phosphorus deficiency stress. Transcriptomic analyses revealed that BR application altered the expression of genes involved in mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, and nitrogen and phosphorus metabolisms under phosphorus deficient condition. Further gene ontology (GO) analysis indicated a significant enrichment of genes associated with reactive oxygen species scavenging process. Ectopic expression of potato brassinosteroid synthesis gene StCYP85A1 in Arabidopsis improved the resistance of transgenic plants to phosphorus deficiency stress, as indicated by the increased germination greening ratio and root growth. Quantitative real time PCR and antioxidant enzyme activity analysis revealed that ectopic expression of StCYP85A1 altered the expression of genes related to nitrogen and phosphorus metabolism, and promoted antioxidant enzyme activity in transgenic plants. These findings indicated that BR improved the tolerance of potato plants to phosphorus deficiency stress by regulating nutrient homeostasis and reactive oxygen species scavenging.

N-acetylcysteine, a small molecule scavenger of reactive oxygen species, alleviates cardiomyocyte damage by regulating OPA1-mediated mitochondrial quality control and apoptosis in response to oxidative stress.

Oxidative stress-induced mitochondrial damage is the major cause of cardiomyocyte dysfunction. Therefore, the maintenance of mitochondrial function, which is regulated by mitochondrial quality control (MQC), is necessary for cardiomyocyte homeostasis. This study aimed to explore the underlying mechanisms of N-acetylcysteine (NAC) function and its relationship with MQC. A hydrogen peroxide-induced oxidative stress model was established using H9c2 cardiomyocytes treated with or without NAC prior to oxidative stress stimulation. Autophagy with light chain 3 (LC3)-green fluorescent protein (GFP) assay, reactive oxygen species (ROS) with the 2',7'-dichlorodi hydrofluorescein diacetate (DCFH-DA) fluorescent, lactate dehydrogenase (LDH) release assay, adenosine triphosphate (ATP) content assay, and a mitochondrial membrane potential detection were used to evaluate mitochondrial dynamics in H2O2-treated H9c2 cardiomyocytes, with a focus on the involvement of MQC regulated by NAC. Cell apoptosis was analyzed using caspase-3 activity assay and Annexin V-fluorescein isothiocyanate (V-FITC)/propidium iodide (PI) double staining. We observed that NAC improved cell viability, reduced ROS levels, and partially restored optic atrophy 1 (OPA1) protein expression under oxidative stress. Following transfection with a specific OPA1-small interfering RNA, the mitophagy, mitochondrial dynamics, mitochondrial functions, and cardiomyocyte apoptosis were evaluated to further explore the mechanisms of NAC. Our results demonstrated that NAC attenuated cardiomyocyte apoptosis via the ROS/OPA1 axis and protected against oxidative stress-induced mitochondrial damage via the regulation of OPA1-mediated MQC. NAC ameliorated the injury to H9c2 cardiomyocytes caused by H2O2 by promoting the expression of OPA1, consequently improving mitochondrial function and decreasing apoptosis.

Effects and medical application of plant-origin polyphenols: A narrative review

The impact of oxidative stress in the pathogenesis of various diseases is well known. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of a biological system to detoxify these reactive intermediates or repair the resulting damage. Polyphenols, a diverse group of compounds with antioxidant properties, help reduce damage by ROS. They are abundant in fruits, vegetables, tea, coffee, wine, and other plant-based foods. The mechanisms of their antioxidant activity are related to their ability to regulate cellular signaling pathways, metal chelation, and mitochondrial protection, while modulating antioxidant enzyme activity and exhibiting anti-inflammatory effects. Polyphenols can also reduce oxidative stress through ROS scavenging, direct neutralization, or enhancing antioxidant defenses within cells. It has been established that polyphenols derived from plant compounds do not harm the metabolism of normal cells, but are involved in modulating the metabolic pathways of diseased cells, which is related to their high redox sensitivity. Incorporating polyphenol-rich foods into the diet is beneficial for maintaining overall health and reducing the risk of oxidative stress-related diseases. Researchers are exploring the therapeutic potential of polyphenols as dietary supplements or functional foods in medical applications. This review discusses the origin, structure, benefits, and application of plant polyphenols in medicine and the food industry. Keywords: biologically active compounds, polyphenols, oxidative stress, antioxidant activity, functional food.

Improving treatment for Parkinson's disease: Harnessing photothermal and phagocytosis-driven delivery of levodopa nanocarriers across the blood-brain barrier

Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB. Furthermore, levodopa metabolism generates reactive oxygen species (ROS), exacerbating neuronal damage. Systemic pulsatile dosing further disrupts natural physiological buffering mechanisms. In this investigation, we devised a ROS-responsive levodopa prodrug system capable of releasing the drug and reducing ROS levels in the central nervous system. The prodrug was incorporated within second near-infrared region (NIR-II) gold nanorods (AuNRs) and utilized angiopep-2 (ANG) for targeted delivery across the BBB. The processes of tight junction opening and endocytosis facilitated improved levodopa transport. ROS scavenging helped alleviate neuronal oxidative stress, leading to enhanced behavioral outcomes and reduced oxidative stress levels in a mouse model of PD. Following treatment, the PD mouse model exhibited enhanced flexibility, balance, and spontaneous exploratory activity. This approach successfully alleviated the motor impairments associated with the disease model. Consequently, our strategy, utilizing NIR-Ⅱ AuNRs and ANG-mediated BBB penetration, coupled with the responsive release of levodopa, offers a promising approach for dopamine supplementation and microenvironmental regulation. This system holds substantial potential as an efficient platform for delivering neuroprotective drugs and advancing PD therapy.

SlLTPg1, a tomato lipid transfer protein, positively regulates in response to biotic stresses

Late blight, caused by Phytophthora infestans (P. infestans), is among the most devastating diseases affecting tomato and other Solanaceae species. Lipid transfer proteins (LTPs) represent a class of small, basic proteins that play a crucial role in combating biotic stresses. Previous studies have shown that SlLTPg1 most strongly responds after P. infestans infestation among the LTPs family in tomato. However, the function of SlLTPg1 in disease resistance remains unclear. Here, we constructed transient overexpression and VIGS-silenced plants of SlLTPg1. Our results revealed that SlLTPg1 plays a regulatory role in enhancing tomato resistance against P. infestans. This enhancement was attributed to the upregulation of defense-related genes and reactive oxygen species (ROS) scavenging genes, as well as increased enzymatic antioxidant activities. Importantly, we found that the SlLTPg1 protein significantly inhibited the growth of Fusarium oxysporum (F. oxysporum) by observing the zone of inhibition. Interestingly, we found smaller lesion diameters and upregulated expression levels of PR genes in transient overexpression SlLTPg1 of tobacco. Therefore, we further constructed transgenic tobacco lines of SlLTPg1, presenting evidence that overexpression of SlLTPg1 could positively regulate the resistance of tobacco to F. oxysporum. These findings revealed the role of SlLTPg1 in tomato resistance to P. infestans and tobacco resistance to F. oxysporum. Moreover, we propose SlLTPg1 as a potential candidate gene for augmenting broad-spectrum plant resistance against pathogens.