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The wound repair process usually leads to a non-functioning mass of fibrotic tissue because of the oxidative imbalance of deep tissue layers. However, how to improve the penetration of active ingredients into deeper layers and regulate oxidative imbalances to create a regenerative microenvironment still remains a challenge. In this study, we designed a novel tetrahedral-framework nucleic acid (tFNA) nanozyme that could penetrate the skin/mucosa barrier as deep as 450 μm within 24 h. We also demonstrated the protective role of tFNAs on the mitochondrial structural and functional integrity and inhibition of reactive oxygen species production to repair oxidative imbalances through ERK1/2-Nrf2-HO-1 during repair processes. It was found that the proliferative state and the migration ability of postburn cells in vitro were accelerated, and the early closure of wounds in vivo was significantly promoted. This study therefore provides a promising strategy to efficiently regulate the oxidative imbalances in the deep layers of the skin during wound healing. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity. [ABSTRACT FROM AUTHOR]

Red blood cells respond to fluctuations in blood plasma pH by changing the rate of biochemical and physical processes that affect the specific functions of individual cells. This study aimed to analyze the effect of pH changes on red blood cell morphology and structure. The findings revealed that an increase or decrease in pH above or below the physiological level of pH 7.4 results in the transformation of discocytes into echinocytes and causes significant alterations in the membrane, including its roughness, cytoskeleton structure, and the cell's elastic modulus. Furthermore, the study shown a strong connection between critical acidosis and alkalosis with increased intracellular reactive oxygen species production. [ABSTRACT FROM AUTHOR]

Pulmonary artery endothelial cells (PAECs) are a major contributor to hypoxic pulmonary hypertension (PH) due to the possible roles of reactive oxygen species (ROS). However, the molecular mechanisms and functional roles of ROS in PAECs are not well established. In this study, we first used Amplex UltraRed reagent to assess hydrogen peroxide (H2O2) generation. The result indicated that hypoxic exposure resulted in a significant increase in Amplex UltraRed-derived fluorescence (i.e., H2O2 production) in human PAECs. To complement this result, we employed lucigenin as a probe to detect superoxide (O2−) production. Our assays showed that hypoxia largely increased O2− production. Hypoxia also enhanced H2O2 production in the mitochondria from PAECs. Using the genetically encoded H2O2 sensor HyPer, we further revealed the hypoxic ROS production in PAECs, which was fully blocked by the mitochondrial inhibitor rotenone or myxothiazol. Interestingly, hypoxia caused an increase in the migration of PAECs, determined by scratch wound assay. In contrast, nicotine, a major cigarette or e-cigarette component, had no effect. Moreover, hypoxia and nicotine co-exposure further increased migration. Transfection of lentiviral shRNAs specific for the mitochondrial Rieske iron–sulfur protein (RISP), which knocked down its expression and associated ROS generation, inhibited the hypoxic migration of PAECs. Hypoxia largely increased the proliferation of PAECs, determined using Ki67 staining and direct cell number accounting. Similarly, nicotine caused a large increase in proliferation. Moreover, hypoxia/nicotine co-exposure elicited a further increase in cell proliferation. RISP knockdown inhibited the proliferation of PAECs following hypoxia, nicotine exposure, and hypoxia/nicotine co-exposure. Taken together, our data demonstrate that hypoxia increases RISP-mediated mitochondrial ROS production, migration, and proliferation in human PAECs; nicotine has no effect on migration, increases proliferation, and promotes hypoxic proliferation; the effects of nicotine are largely mediated by RISP-dependent mitochondrial ROS signaling. Conceivably, PAECs may contribute to PH via the RISP-mediated mitochondrial ROS. [ABSTRACT FROM AUTHOR]

Viruses are intracellular parasites that utilize organelles, signaling pathways, and the bioenergetics machinery of the cell to replicate the genome and synthesize proteins to build up new viral particles. Mitochondria are key to supporting the virus life cycle by sustaining energy production, metabolism, and synthesis of macromolecules. Mitochondria also contribute to the antiviral innate immune response. Here, we describe the different mechanisms involved in virus–mitochondria interactions. We analyze the effects of viral infections on the metabolism of glucose in the Warburg phenotype, glutamine, and fatty acids. We also describe how viruses directly regulate mitochondrial function through modulation of the activity of the electron transport chain, the generation of reactive oxygen species, the balance between fission and fusion, and the regulation of voltage-dependent anion channels. In addition, we discuss the evasion strategies used to avoid mitochondrial-associated mechanisms that inhibit viral replication. Overall, this review aims to provide a comprehensive view of how viruses modulate mitochondrial function to maintain their replicative capabilities. [ABSTRACT FROM AUTHOR]

Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity. [ABSTRACT FROM AUTHOR]

From quiescence to activation and myogenic differentiation, muscle stem cells (MuSCs) experience drastic alterations in their signaling activity and metabolism. Through balanced cycles of fission and fusion, mitochondria alter their morphology and metabolism, allowing them to affect their decisive role in modulating MuSC activity and fate decisions. This tightly regulated process contributes to MuSC regulation by mediating changes in redox signaling pathways, cell cycle progression, and cell fate decisions. In this review, we discuss the role of mitochondrial dynamics as an integral modulator of MuSC activity, fate, and maintenance. Understanding the influence of mitochondrial dynamics in MuSCs in health and disease will further the development of therapeutics that support MuSC integrity and thus may aid in restoring the regenerative capacity of skeletal muscle. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) infection is characterized by febrile illness, severe joint pain, myalgia, and cardiovascular complications. Given that CHIKV stimulates reactive oxygen species (ROS) and pro- and anti-inflammatory cytokines, events that disrupt vascular homeostasis, we hypothesized that CHIKV induces arterial dysfunction by directly impacting redox-related mechanisms in vascular cells. Wild-type (WT) and iNOS knockout (iNOS−/−) mice were administered either CHIKV (1.0 × 106 PFU/µL) or Mock vehicle via the intracaudal route. In vivo, CHIKV infection induced vascular dysfunction (assessed by a wire myograph), decreased systolic blood pressure (tail-cuff plethysmography), increased IL-6 and IFN-γ, but not TNF-α levels (determined by ELISA), and increased protein content by Western blot. Marked contractile hyporesponsiveness to phenylephrine was observed 48 h post-infection, which was restored by endothelium removal. L-NAME, 1400W, Tiron, and iNOS gene deletion prevented phenylephrine hyporesponsiveness. CHIKV infection increased vascular nitrite concentration (Griess reaction) and superoxide anion (O2•−) generation (lucigenin chemiluminescence), and decreased hydrogen peroxide (H2O2, by Amplex Red) levels 48 h post-infection, alongside increased TBARS levels. In vitro, CHIKV infected endothelial cells (EA.hy926) and upregulated ICAM-1 and iNOS protein expression (determined by Western blot). These data support the conclusion that CHIKV-induced alterations in vascular ROS/NF-kB/iNOS/NO signaling potentially contribute to cardiovascular events associated with Chikungunya infection. [ABSTRACT FROM AUTHOR]

17β-estradiol plays a crucial role in regulating cellular processes in both reproductive and non-reproductive tissues, including the thyroid gland. It modulates oxidative stress and contributes to sexual dimorphism in thyroid diseases, with ROS production, particularly H2O2, generated by NOX/DUOX enzymes. This study aimed to investigate the effects of 17β-estradiol (10 nM or 100 nM) on the expression of NOX/DUOX, thyroid-specific genes, and endoplasmic reticulum (ER) stress-related genes in male and female porcine thyroid follicular cells. Expression of the studied genes was evaluated by RT-PCR before and after treatment with 17β-estradiol alone or with the addition of NOX4 inhibitor (GKT-136901). Additionally, the level of ROS was measured by flow cytometry analysis. Our results show that 17β-estradiol significantly upregulates thyroid-specific genes, particularly TPO, and stimulates NOX/DUOX expression, affecting the redox state of thyroid cells. It also stimulates ER stress-related genes such as CHOP. In conclusion, estrogen excess may contribute to thyroid disease development via such possible mechanisms as the upregulation of key thyroid-specific genes, particularly TPO, and of genes involved in the cellular response to ER stress, especially CHOP, as well as by the stimulation of the NOX/DUOX system with consequent ROS overproduction. These mechanisms may play a certain role in the higher prevalence of thyroid diseases in women. [ABSTRACT FROM AUTHOR]

Scientists are searching for reactive oxygen species, which have been associated with various health issues like heart problems, neurological disorders, inflammation, and aging. Salen complexes have proven to be effective in multiple oxidative stress situations and have been used as catalase and superoxide mimetics. To explore this further, three mixed complexes were synthesized using a Schiff base (salen) and a sugar (d-glucose) with Co(II), Ni(II), and Cu(II) ions. These complexes were then diagnosed by different analytical and spectral techniques. Stoichiometry, stereochemistry, some physical properties, and the method of bonding complexes were measured. Comparisons of the IR and 1HNMR spectra of the ligands with the complexes demonstrated the involvement of the azomethine group of the ligand in the chelation process. The mass spectra and TGA agree with the proposed formula of the complexes, and the conductivity and UV–Vis data supported the octahedral geometry of the complexes, and information was obtained from partial parameter calculations by molecular modeling. The metal complexes exhibited strong antimicrobial and antioxidant properties when compared to standard drugs. The like-superoxide and catalyst mimetic complexes were screened using DPPH ABTS, revealing their effectiveness. [ABSTRACT FROM AUTHOR]

Catheter-associated urinary tract infections (CAUTIs) present significant health risks in medical settings, necessitating innovative solutions to prevent bacterial colonization on catheter surfaces. This study introduces a novel polymeric coating with dual antifouling and light-activated bactericidal properties to enhance the bactericidal efficacy of urinary catheters. The coatings were synthesized using a one-step process involving pyrogallol chemistry to deposit a copolymer composed of zwitterionic sulfobetaine for antifouling and sodium copper chlorophyllin, a photosensitizer that generates reactive oxygen species under light exposure to effectively kill bacteria. We evaluated the antifouling properties, cytocompatibility, and bactericidal performance of the coatings under various light conditions. The results showed significant reductions in bacterial adhesion, with light activation further endowing the catheter with bactericidal effects. Additionally, light could be delivered through an optical fiber within the catheter lumen to target and kill bacteria. The innovative coating using light-activated bactericidal action offers a promising approach to preventing CAUTIs, representing a potential breakthrough in developing safer and more effective urinary catheters. [ABSTRACT FROM AUTHOR]

Simple Summary: The International Agency for Research on Cancer (IARC) projects that by 2040, the global incidence of cancer would reach 27.5 million new cases. The current primary modalities of cancer treatment encompass surgery, radiation, and chemotherapy, which can harm normal tissues or fail to fully eliminate cancer. Nanomaterials make it easier to keep an eye on surgeries that remove tumors, deliver chemotherapy directly and selectively to cancer cells and neoplasms, and make radiation therapy more effective. It mitigates the risk and enhances the survival of cancer patients. This review aims to consolidate various metal peroxide nanomaterials utilized in cancer treatment with a special emphasis on metal peroxide nanoparticle surface modification for enhancing the efficacy of nanomaterials in tumor microenvironment. Researchers can acquire knowledge regarding metal peroxide nanoparticle types, their mechanisms of action, and their contributions to existing cancer medicines for enhanced cancer management. Background: The significant expansion of nanobiotechnology and nanomedicine has led to the development of innovative and effective techniques to combat various pathogens, demonstrating promising results with fewer adverse effects. Metal peroxide nanoparticles stand out among the crucial yet often overlooked types of nanomaterials, including metals. These nanoparticles are key in producing oxygen (O2) and hydrogen peroxide (H2O2) through simple chemical reactions, which are vital in treating various diseases. These compounds play a crucial role in boosting the effectiveness of different treatment methods and also possess unique properties due to the addition of metal ions. Methods: This review discusses and analyzes some of the most common metal peroxide nanoparticles, including copper peroxide (CuO2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), barium peroxide (BaO2), and titanium peroxide (TiOx) nanosystems. These nanosystems, characterized by their greater potential and treatment efficiency, are primarily needed in nanomedicine to combat various harmful pathogens. Researchers have extensively studied the effects of these peroxides in various treatments, such as catalytic nanotherapeutics, photodynamic therapy, radiation therapy, and some combination therapies. The tumor microenvironment (TME) is particularly unique, making the impact of nanomedicine less effective or even null. The presence of high levels of reactive oxygen species (ROS), hypoxia, low pH, and high glutathione levels makes them competitive against nanomedicine. Controlling the TME is a promising approach to combating cancer. Results: Metal peroxides with low biodegradability, toxicity, and side effects could reduce their effectiveness in treating the TME. It is important to consider the distribution of metal peroxides to effectively target cancer cells while avoiding harm to nearby normal cells. As a result, modifying the surface of metal peroxides is a key strategy to enhance their delivery to the TME, thereby improving their therapeutic benefits. Conclusions: This review discussed the various aspects of the TME and the importance of modifying the surface of metal peroxides to enhance their therapeutic advantages against cancer, as well as address safety concerns. Additionally, this review covered the current challenges in translating basic research findings into clinical applications of therapies based on metal peroxide nanoparticles. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is a hallmark of cancer cachexia (CC). Mitochondrial reactive oxygen species (ROS) are elevated in muscle shortly after tumor onset. Targeting mitochondrial ROS may be a viable option to prevent CC. The aim of this study was to evaluate the efficacy of a mitochondria-targeted antioxidant, SkQ1, to mitigate CC in both biological sexes. Male and female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells (total 1 × 106 cells) or PBS (equal volume control). SkQ1 was dissolved in drinking water (∼250 nmol/kg body wt/day) and administered to mice beginning 7 days following tumor induction, whereas control groups consumed normal drinking water. In vivo muscle contractility of dorsiflexors, deuterium oxide-based protein synthesis, mitochondrial respiration and mRNA content of mitochondrial, protein turnover, and calcium channel-related markers were assessed at endpoint (25 days following tumor induction). Two-way ANOVAs, followed by Tukey's post hoc test when interactions were significant (P ≤ 0.05), were performed. SkQ1 attenuated cancer-induced atrophy, promoted protein synthesis, and abated Redd1 and Atrogin induction in gastrocnemius of C26 male mice. In female mice, SkQ1 decreased muscle mass and increased catabolic signaling in the plantaris of tumor-bearing mice, as well as reduced mitochondrial oxygen consumption, regardless of tumor. However, in females, SkQ1 enhanced muscle contractility of the dorsiflexors with concurrent induction of Ryr1, Serca1, and Serca2a in TA. In conclusion, the mitochondria-targeted antioxidant SkQ1 may attenuate CC-induced muscle loss in males, while improving muscle contractile function in tumor-bearing female mice, suggesting sexual dimorphism in the effects of this mitochondrial therapy in CC. NEW & NOTEWORTHY: Herein, we assess the efficacy of the mitochondria-targeted antioxidant SkQ1 to mitigate cancer cachexia (CC) in both biological sexes. We demonstrate that SkQ1 administration attenuates muscle wasting induced by C26 tumors in male, but not female, mice. Conversely, we identify that in females, SkQ1 improves muscle contractility. These phenotypic adaptations to SkQ1 are aligned with respective responses in muscle protein synthesis, mitochondrial respiration, and mRNA content of protein turnover, as well as mitochondrial and calcium handling-related markers. [ABSTRACT FROM AUTHOR]

Intervertebral disk degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, potentially contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; however, its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its underlying mechanisms. Nucleus pulposus (NP) tissues were collected from patients, and ECM stiffness, reactive oxygen species (ROS) levels, apoptosis rates, and P65 expression in these tissues with varying Pfirrmann scores were determined. In vitro experiments were conducted to investigate the effects of melatonin on various pathophysiological mechanisms within the NP cells cultured on soft substrates with differing stiffness levels. Our findings revealed a positive correlation between ECM stiffness in human NP tissue and degree of IVDD. In addition, phosphorylation of P65 exhibited a strong association with matrix stiffness. Enhanced levels of ROS and cellular apoptosis were observed within degenerated intervertebral disks. In vitro experiments demonstrated that melatonin significantly inhibited catabolism and apoptosis induced by stiff matrices, along with elevated ROS levels. Furthermore, we observed that melatonin inhibited NP cell catabolism and apoptosis by reducing the melatonin receptors mediated activation of the PI3K/AKT and nuclear factor-kappa B (NF-κB) pathways. Also, we found that the reduction of ROS by melatonin can assist in inhibiting the activation of the NF-κB pathway. The outcomes of the in vivo experiments corroborated the results of the in vitro experiments, illustrating that melatonin treatment could alleviate the compression-induced upregulation of matrix stiffness in NP and IVDD. Collectively, melatonin can potentially alleviate high matrix stiffness-induced IVDD by reducing intracellular ROS levels and inhibiting the PI3K/AKT/NF-κB pathway. NEW & NOTEWORTHY: Melatonin mitigates intervertebral disk degeneration (IVDD) induced by matrix stiffness through reactive oxygen species (ROS) reduction. Matrix stiffness is related to increased nucleus pulposus cell ROS, apoptosis, and degeneration. Melatonin inhibits PI3K/AKT/NF-κB pathways via melatonin receptors in a stiff matrix environment. In vivo, melatonin restores disk height and alleviates IVDD progression. [ABSTRACT FROM AUTHOR]

Plant growth and productivity are continually being challenged by a diverse array of abiotic stresses, including: water scarcity, extreme temperatures, heavy metal exposure, and soil salinity. A common theme in these stresses is the overproduction of reactive oxygen species (ROS), which disrupts cellular redox homeostasis causing oxidative damage. Ascorbic acid (AsA), commonly known as vitamin C, is an essential nutrient for humans, and also plays a crucial role in the plant kingdom. AsA is synthesized by plants through the d-mannose/l-galactose pathway that functions as a powerful antioxidant and protects plant cells from ROS generated during photosynthesis. AsA controls several key physiological processes, including: photosynthesis, respiration, and carbohydrate metabolism, either by acting as a co-factor for metabolic enzymes or by regulating cellular redox-status. AsA's multi-functionality uniquely positions it to integrate and recalibrate redox-responsive transcriptional/metabolic circuits and essential biological processes, in accordance to developmental and environmental cues. In recognition of this, we present a systematic overview of current evidence highlighting AsA as a central metabolite-switch in plants. Further, a comprehensive overview of genetic manipulation of genes involved in AsA metabolism has been provided along with the bottlenecks and future research directions, that could serve as a framework for designing "stress-smart" crops in future. [ABSTRACT FROM AUTHOR]

This work was devoted to the investigation of the contribution of various species in plasma to styrene decomposition. Different background gases (air, argon, nitrogen, and oxygen) and plasma reactor (in‐plasma, post‐plasma, and post‐plasma with buffer tube) were employed in this experiment. The results showed that degradation and polymerization of styrene occur simultaneously in the plasma treatment process. In the discharge zone, the bombardment of electrons and energetic particles on styrene and its degradation intermediates played a role in breaking its weak bond energy and promoting their conversion. The short‐lived reactive species with high oxidation potential in plasma were the prerequisite for complete degradation of styrene, due to its ability of breaking bonds with large bond energies, such as benzene ring. Away from the discharge zone, long‐lived reactive oxygen species further oxidized and degraded styrene, and its intermediates outside the discharge zone, promoting their mineralization. [ABSTRACT FROM AUTHOR]

Highlights: Cynarin decreases neuroinflammation levels and attenuates microglial pyroptosis. Cynarin hinders the formation of NLRP3 inflammasome through Nrf2-dependent expression. Cynarin-treated mice showed lower levels of reactive oxygen species (ROS) and cell death, as well as reduced neurohistological damage, and improved hindlimb locomotor function compared to untreated mice. Background: Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy. Methods: Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and pyroptosis to promote neurological recovery after SCI. Results: Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of reactive oxygen species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial pyroptosis and neuroinflammation. Conclusions: To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 inhibitor for microglia in neuropathies. [ABSTRACT FROM AUTHOR]

Proton therapy is used to eradicate tumors in sensitive areas by targeted delivery of energy. Its effectiveness can be amplified using nanoparticles (NPs) as sensitizers, due to the production of reactive oxygen species at the NP's catalytically active surface, causing the cleavage of DNA. However, the impact of stabilizing macromolecular ligands capping the particles, needed for nanosensitizer dispersion in physiological fluids, is underexplored. Herein, ligand‐free colloidal platinum NPs (PtNPs) fabricated by scalable laser synthesis in liquids are used, which allows studying particle and ligand effects separately. PtNPs are incubated with stabilizing concentrations of the clinically approved ligands albumin, Tween, and polyethylene glycol, and irradiated with proton beams at clinically relevant doses (2 and 5 Gy). At these doses, plasmid DNA cleavage larger than 55% of clustered DNA damage is achieved. Bovine serum albumin, Tween, and polyethylene glycol on the NP surface work as double‐strand breaks (DSB) enhancers and synergetic effects occur even at low and clinically relevant particle concentrations and irradiation doses. Here, DSB enhancement by ligand‐capped PtNP even exceeds the sum of the individual ligand and particle effects. The presented fundamental correlations provide selection rules for nanosensitizer design in proton therapy. [ABSTRACT FROM AUTHOR]

DNA origami nanostructures are promising carries for drug delivery applications. However, their limited stability under relevant conditions often presents a challenge. Herein, the structural stability of DNA origami nanostructures is investigated in a setting compatible with their application in photodynamic therapy (PDT). To this end, DNA origami triangles and six‐helix bundles (6HBs) are loaded with the clinically tested photosensitizer methylene blue, which upon irradiation with red light generates reactive oxygen species (ROS) that attack the DNA origami nanostructures. ROS‐induced structural damage is observed to depend on the ionic composition of the surrounding medium and becomes more severe at low ionic strength. Mg2+ ions can efficiently protect the DNA origami nanostructures from ROS‐induced damage and may even heal some of the damage obtained under Mg2+‐free conditions when added after irradiation. Finally, the employed DNA origami 6HBs are more resistant toward ROS‐induced structural damage than the triangles, which is attributed to their markedly different mechanical properties. These results thus provide some fundamental insights into the stabilizing role of DNA origami superstructure that may guide the selection or design of DNA origami nanocarriers with optimized stability for their application in PDT. [ABSTRACT FROM AUTHOR]

Mitochondria are vital for retinal cell function and survival, and there is growing evidence linking mitochondrial dysfunction to retinal degenerations. Although ARL3 mutations have been linked to multiple forms of retinal degeneration, the relationship between ARL3 and mitochondria remains unexplored. Herein, we investigated the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F mutations on mitochondrial function in fibroblasts obtained from patients with ARL3‐related rod‐cone dystrophy. Our findings revealed that these mutations led to a decrease in mitochondrial respiration, an increase in the accumulation mitochondrial reactive oxygen species (ROS), and induction of apoptosis in fibroblasts. Additionally, we conducted a comparative analysis of the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F proteins on mitochondria in ARPE‐19 cells. Results showed that ARL3T31A and ARL3T31A/C118F not only affected mitochondrial function but also induced apoptosis in ARPE‐19 cells. Conversely, ARL3C118F primarily influenced cell apoptosis with minimal effects on mitochondrial function in ARPE‐19 cells. Transcriptome analysis further suggested the involvement of respiratory electron transport, response to ROS, and apoptotic signaling pathways in ARL3T31A/C118F cells. Our study demonstrated that ARL3‐related mutations play a significant role in the diversity of mitochondrial function, providing novel insights into the functional analysis of ARL3‐related mutations. [ABSTRACT FROM AUTHOR]

Rice bran oil is a type of rice oil made by leaching or pressing during rice processing and has a high absorption rate after consumption. When oxidative rancidity occurs, it may cause oxidative stress (OS) and affect intestinal function. Meanwhile, the toxic effects of oxidised rice bran oil have been less well studied in pigs. Therefore, the IPEC‐J2 cells model was chosen to explore the regulatory mechanisms of oxidised rice bran oil on OS and apoptosis. Oxidised rice bran oil extract treatment (OR) significantly decreased the viability of IPEC‐J2 cells. The results showed that OR significantly elevated apoptosis and reactive oxygen species levels and promoted the expression of pro‐apoptotic gene Caspase‐3 messenger RNA levels. The activation of Nrf2 signalling pathway by OR decreased the cellular antioxidant capacity. This was further evidenced by the expression of kelch‐like ECH‐associated protein 1, heme oxygenase 1, NADH: quinone oxidoreductase 1, superoxide dismutase 2 and heat shock 70 kDa protein genes and proteins were all downregulated. In conclusion, our results suggested that oxidised rice bran oil induced damage in IPEC‐J2 cells through the Nrf2 signalling pathway. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) therapy has been proven to effectively inhibit the growth of subcutaneous tumors. However, there is no research to explain how plasma‐induced anticancer effects can be transmitted to cancer cells through normal cells. Here, we monitored the effects of plasma‐irradiated HaCaT cells on nonirradiated A375 and HaCaT cells in terms of cell viability and intracellular reactive oxygen species levels in vitro. The experimental results indicated that plasma irradiation may induce plasma‐irradiated HaCaT cells to release soluble factors into the cell culture medium, thereby selectively killing nonirradiated A375 cells. The plasma‐generated short‐lived species play a crucial role in the release of soluble factors. Our research showed that plasma‐induced anticancer effects can be transmitted to deep nonirradiated cancer cells through plasma‐irradiated normal cells. [ABSTRACT FROM AUTHOR]

Objective OA is a chronic disease characterized by cartilage degeneration and inflammation, with no approved disease-modifying drugs. This study aimed to identify pathogenic genes and elucidate their mechanism in OA. Methods We systematically identified pathogenic genes combined sing-cell and bulk transcriptome profiles of cartilage tissues in OA. Adenovirus carrying the serpin peptidase inhibitor clade E member 2 (serpinE2) or exogenous serpinE2 was injected into monosodium iodoacetate (MIA)-induced OA-model rats. Histological analysis, immunohistochemistry and Alcian blue staining were performed. In vitro , immunofluorescence, quantitative real-time PCR (RT-qPCR), ELISA and western blot assays were performed. Results serpinE2 exhibited elevated expression and hypomethylation, showing a positive association with collagen pathway activities in patients with OA. Silencing serpinE2 aggravated MIA-induced knee cartilage degeneration in OA-model rats. Conversely, the intra-articular injection of exogenous serpinE2 ameliorated articular cartilage degeneration, reduced pain-related behavioural responses and relieve synovitis in MIA-induced OA-model rats. Exogenous serpinE2 not only attenuated the elevation of NLRP3, IL-1β and caspase1 expression levels but also restored the reduction in cell viability induced by lipopolysaccharide (LPS) in chondrocytes. Mechanistically, we found that exogenous serpinE2 inhibited LPS-induced reactive oxygen species (ROS) release and NF-κB signalling activation. Conclusions serpinE2 plays a protective role in cartilage and synovium tissues, suggesting that serpinE2 gene transfer or molecules that upregulate serpinE2 expression could be therapeutic candidates for OA. [ABSTRACT FROM AUTHOR]

Licochalcone A (Lico A), a naturally bioactive flavonoid, has shown antitumor activity in several types of cancers. However, few studies have focused on its effect on acute myeloid leukemia (AML). Cell viability and colony formation potential were detected by CCK-8 assay and colony formation assay, respectively. Cell cycle distribution and apoptosis were assessed by flow cytometry. Ferroptosis was assessed by measuring reactive oxygen species (ROS), lipid ROS, malondialdehyde (MDA), and glutathione (GSH). Protein expression levels were determined by immunoblotting and immunohistochemistry (IHC), and mRNA expression was detected by real-time qPCR. The m6A modification of MDM2 mRNA was verified by methylated RNA immunoprecipitation (MeRIP) assay, and the interaction of IGF2BP3 and MDM2 mRNA was analyzed by RIP assay. Actinomycin D was used to evaluate mRNA stability. The efficacy of Lico A in vivo was examined by a murine xenograft model. Lico A suppressed cell proliferation and induced ferroptosis in MOLM-13 and U-937 in vitro, and slowed the growth of xenograft tumors in vivo. IGF2BP3 was highly expressed in human AML specimens and cells, and Lico A suppressed IGF2BP3 expression in AML cells. Lico A exerted the anti-proliferative and pro-ferroptosis effects by downregulating IGF2BP3. Moreover, IGF2BP3 enhanced the stability and expression of MDM2 mRNA through an m6A-dependent manner. Downregulation of IGF2BP3 impeded AML cell proliferation and enhanced ferroptosis via repressing MDM2. Furthermore, Lico A could affect the MDM2/p53 pathway by downregulating IGF2BP3 expression. Lico A exerts the anti-proliferative and pro-ferroptosis activity in AML cells by affecting the IGF2BP3/MDM2/p53 pathway, providing new evidence for Lico A as a promising agent for the treatment of AML. [ABSTRACT FROM AUTHOR]

Eukaryotic cells respond to stress by altering coding and non‐coding gene expression programs. Alongside many approaches and regulatory mechanisms, long non‐coding RNAs (lncRNA) are finding a significant place in gene regulation, suggesting an involvement in various cellular processes and pathophysiology. LncRNAs are regulated by many transcription factors, including SMAR1 and p53, which are tumor suppressor genes. SMAR1 inhibits cancer cell metastasis and invasion and is also known to inhibit apoptosis during low‐dose stress in coordination with p53. Data mining analysis suggested that these tumor suppressor genes might coregulate the lncRNA RP11‐431M3.1 in colon cancer cells. Importantly, RP11‐431M3.1 expression was found to be negatively correlated with patient survival rates in a number of cancers. Oxidative stress occurs when an imbalance in the body is caused by reactive oxygen species (ROS). This imbalance is known to be important in the development/pathogenesis of colon cancer. We are researching the role and control of this lncRNA in HCT116 cells under conditions of oxidative stress. We observed a dose‐dependent differential expression of lncRNA upon H2O2 treatment and found that p53 and SMAR1 bind differentially to the promoter in response to the dose of stress inducer used. RP11‐431M3.1 was observed to sponge miR‐138 which has an important target gene, hypoxia‐inducible factor (HIF1A). miR‐138 was observed to bind differentially to RP11‐431M3.1 and HIF1A RNA depending on the dose of oxidative stress. Furthermore, the knockdown of RP11‐431M3.1 decreased the migration and proliferation of colon cancer cells. Our results suggest a previously undescribed regulatory mechanism through which RP11‐431M3.1 is transcriptionally regulated by SMAR1 and p53, target HIF1A through miR‐138, and highlight its potential as a therapeutic and diagnostic marker for cancer. [ABSTRACT FROM AUTHOR]

Cellular senescence is described as an irreversible cell cycle arrest for proliferating cells and is associated with the secretion of senescence associated secretory phenotype factors. It has been known to accumulate with age and is regarded as a key driver of aging‐associated skin pathologies. However, the lack of markers of skin senescence and partially understood skin cellular senescence mechanisms has limited the exploration of skin aging and anti‐skin aging strategies. Recently, intracellular calcium signaling has emerged as an important regulator of cellular senescence and aging. However, little is known about the modulation of skin cellular senescence by calcium‐associated factors. Here, we found that the expression of calcium channel transient receptor potential melastatin 7 (TRPM7) is elevated during skin keratinocyte senescence and aging. Importantly, TRPM7 promotes skin keratinocyte senescence by triggering intracellular calcium transfer from the endoplasmic reticulum to the mitochondria; accumulation of mitochondrial calcium then induces a drop in mitochondrial membrane potential and reactive oxygen species production, leading to subsequent nuclear enlargement and DNA damage. Altogether, these findings indicate that TRPM7 controls skin keratinocyte senescence through regulating intracellular calcium signaling, and thus, shed light on novel strategies for anti‐skin aging therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose : Cancer remains one of the leading causes of death globally. In pursuit of alternative treatments, nature-based ones are especially in demand due to the perceived lesser toxicity and cost-effectiveness. Plumbagin, a naphthoquinone compound derived from the Plumbaginaceae family, has demonstrated significant anticancer properties. It is a yellow crystalline phytochemical that exhibits potent cytotoxic effects against various cancer cells in vitro and in vivo. Results : Its distinct anticancer mechanisms include modulating signaling pathways, such as NF-kβ, STAT3, MMP-9, VEGF, and Akt, induction of apoptosis, autophagy, cell cycle regulation etc. Furthermore, plumbagin also induces reactive oxygen species (ROS) generation and causes oxidative DNA damage. An exciting feature of plumbagin is its ability to sensitize chemo and radio resistant cancer cells. Even with significant anticancer potential, plumbagin is yet to be used in clinics due to its high lipophilicity, insolubility in water, short half-life, and low melting point. To conquer these limitations and possible exploitation of this potent natural compound, the scientific community has used several nano-based delivery systems, such as liposomes, niosomes, micelles, microparticles etc. Conclusion : Despite all these promising attributes, rigorous preclinical and clinical evaluations are essential to validate its actual anticancer potential before considering it as one of the mainstream phytotherapeutic agents. [Display omitted] • The current article is a comprehensive summary of anticancer potential of plumbagin in different cancer models. • The mechanism of action of plumbagin affecting different signaling cascade has been highlighted. • Despite their significant therapeutic potential, plumbagin is yet to be exploited in clinics. The reason and troubleshoot have been suggested. • Various nanoformulations of plumbagin have been covered that showed better efficacy compared to free plumbagin. [ABSTRACT FROM AUTHOR]

Aim: Sex‐determining region Y‐related high‐mobility group box 4 (SOX4) has been reported to play a carcinogenic role in endometrial cancer (EC). However, the biological function and regulatory mechanisms of SOX4 in ferroptosis during the progression of EC are still unknown. Methods: The mRNA and protein levels were scrutinized by quantitative reverse‐transcription polymerase chain reaction and western blot, respectively. The cell viability and proliferative capability were determined by cell counting kit‐8 assay and 5‐ethynyl‐2′‐deoxyuridine (EdU) assay. Transcriptional regulation of gene expression was investigated by dual‐luciferase reporter assay and chromatin immunoprecipitation. Ferroptosis was evaluated by detection of reactive oxygen species, malondialdehyde, Fe2+, and ferroptosis‐related proteins. The mice test was implemented to confirm the influence of SOX4 on EC tumor growth and ferroptosis in vivo. Results: We here discovered the elevation of SOX4 in EC tissues and cells. Functionally, SOX4 knockdown hampered proliferation and promoted ferroptosis of EC cells. Mechanistically, SOX4 bound to p53 promoter and inhibited its transcriptional activity in EC cells. In addition, p53 transcriptionally suppressed SLC7A11 expression in EC cells. Downregulation of p53 reverses the effect of SOX4 knockdown on proliferation and ferroptosis of EC cells. Finally, in vivo experiments demonstrated that SOX4 depletion hindered tumor growth and triggered ferroptosis in EC. Conclusions: These findings collectively suggested that SOX4 inhibited ferroptosis and promoted proliferation of EC cells via the p53/SLC7A11 signaling. Our research unveiled a novel regulatory mechanism of ferroptosis in EC, offering promising perspectives for the development of EC therapies. [ABSTRACT FROM AUTHOR]

In the region of slightly acidic pH (рН 5.7), the manganese cluster in oxygen-evolving complex of photosystem II (PSII) is more resistant to exogenous reductants. The effect of such pH on the heat inactivation efficiency of the electron transport chain (O2 evolution and 2,6-dichlorophenolindophenol reduction) in PSII membranes and thylakoid membranes was investigated. Under thylakoid membranes illumination accompanied by lumen acidification, their resistance to heat inactivation increases. In the presence of protonophores, the rate of heat inactivation increases, which seems to be associated not with the protonophore mechanism, but with structural and/or functional changes in membranes. In PSII membrane preparations, the efficiency of the oxygen evolution inhibition at pH 5.7 is also lower than at pH 6.5. The role of reactive oxygen species in thermal inactivation of photosynthetic membranes was investigated using a lipophilic cyclic hydroxylamine ESR spin probe. [ABSTRACT FROM AUTHOR]

Oxidative stress is a primary contributor to cerebral ischemia/reperfusion (CI/R) injury, and the use of antioxidants represents a crucial therapeutic strategy for managing CI/R injury. This study aims to explore the antioxidant effects of benzyl ferulate on CI/R injury and elucidate its underlying mechanisms. In vivo models of CI/R injury and hypoxia/reoxygenation (H/R) injury in SH‐SY5Y cells were established, followed by treatment with benzyl ferulate. The extent of oxidative stress was assessed through evaluations of neurobiological function, cerebral infarct volume, reactive oxygen species (ROS), apoptosis levels, etc. Results indicated that benzyl ferulate significantly downregulated the expression of NADPH oxidase 2 (NOX) 2/NOX4 while upregulating miRNAs (652/532/92b) in CI/R rats or SH‐SY5Y cells. It also reduced total NOX enzyme activity, enhanced superoxide dismutase (SOD) activity, decreased ROS and malondialdehyde (MDA) production, and inhibited cleaved caspase‐3 and Bax expression—ultimately leading to reduced cell apoptosis. Benzyl ferulate effectively mitigates oxidative stress injuries of middle cerebral artery occlusion (MCAO) rats or SH‐SY5Y cells subjected to H/R, and its mechanism appears to involve modulation of the miRNAs (652/532/92b)/NOX2/4 axis. This study first proved that benzyl ferulate is a promising antioxidant candidate for treating CI/R injury. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Though the pathogenesis of AF is complex and is not completely understood, many studies suggest that oxidative stress is a major mechanism in pathophysiology of AF. Through multiple mechanisms, reactive oxygen species (ROS) lead to the formation of an AF substrate that facilitates the development and maintenance of AF. In this review article, we provide an update on the different mechanisms by which oxidative stress promotes atrial remodeling. We then discuss several therapeutic strategies targeting oxidative stress for the prevention or treatment of AF. Considering the complex biology of ROS induced remodeling, and the evolution of ROS sources and compartmentalization during AF progression, there is a definite need for improvement in timing, targeting and reduction of off-target effects of therapeutic strategies targeting oxidative injury in AF. • For this special issue, we provide an update on the mechanisms by which oxidative stress promotes atrial fibrillation (AF). • We then discuss contemporary therapeutic strategies targeting oxidative stress for the prevention or treatment of AF. • Finally, we describe gaps in current knowledge and identify potential targets for novel therapeutic strategies in AF. [ABSTRACT FROM AUTHOR]

Biosensors are powerful tools for real-time monitoring of metabolic state. Low reactive oxygen species (ROS) level and high reductive capacity favor repopulation and chemotherapy resistance of leukemia cells. Either glycolysis or oxidative phosphorylation driven by fatty acid and glutamine supports the development of acute leukemia. Fatty acid synthesis and certain amino acids promote the progression of acute leukemia. Redox metabolism plays a central role in the cellular metabolism network, involves catabolic and anabolic reactions of diverse biomass, and determines the redox state of cells. It can be quantitatively and conveniently measured in living cells and organisms with genetically encoded fluorescent sensors, providing novel insights that cannot be readily acquired via conventional metabolic assays. Here, we review the recent progress on the regulation of leukemogenesis via redox metabolism, especially redox biosensor-based findings. In general, low reactive oxygen species levels and high reductive capacity promote leukemogenesis and chemotherapy resistance in leukemia cells, and acute leukemia cells rewire metabolism of glucose, fatty acids, and some amino acids, together with oxidative phosphorylation, to fuel energy production, support biomass-related synthesis, and survive oxidative stress. In summary, redox metabolism is a potential target for the development of novel therapies for leukemia or beneficial dietary regimens for patients with refractory and relapsed leukemia. [ABSTRACT FROM AUTHOR]

Objective: An imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms is believed to be a critical factor in the development of schizophrenia (SCZ) like neurological illnesses. Understanding the roles of ROS in the development of SCZ and the potential activity of natural antioxidants against SCZ could lead to more effective therapeutic options for the prevention and treatment of the illness. Methods: SCZ is a mental disorder characterised by progressive impairments in working memory, attention, and executive functioning. In present investigation, we summarized the experimental findings for understanding the role of oxidative stress (OS) in the development of SCZ and the potential neuroprotective effects of natural antioxidants in the treatment of SCZ. Results: Current study supports the use of the mentioned antioxidant natural compounds as a potential therapeutic candidates for the treatment of OS mediated neurodegeneration in SCZ. Discussion: Elevated levels of harmful ROS and reduced antioxidant defense mechanisms are indicative of increased oxidative stress (OS), which is associated with SCZ. Previous research has shown that individuals with SCZ, including non-medicated, medicated, first-episode, and chronic patients, exhibit decreased levels of total antioxidants and GSH. Additionally, they have reduced antioxidant enzyme levels such as catalase (CAT), glutathione (GPx), and, superoxide dismutase (SOD) and lower serum levels of brain-derived neurotrophic factor (BDNF) in their brain tissue. The mentioned natural antioxidants may assist in reducing oxidative damage in individuals with SCZ and increasing BDNF expression in the brain, potentially improving cognitive function and learning ability. [ABSTRACT FROM AUTHOR]

This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery. EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, p = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol H2O2/g tisssue/h vs. 15.7 ± 1.55 nmol H2O2/g tisssue/h, p < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

The present investigation aimed to study the cardiovascular responses and the cerebral oxygenation (Cox) during exercise in acute hypoxia and with contemporary mental stress. Fifteen physically active, healthy males (age 29.0 ± 5.9 years) completed a cardiopulmonary test on a cycle ergometer to determine the workload at their gas exchange threshold (GET). On a separate day, participants performed two randomly assigned exercise tests pedaling for 6 min at a workload corresponding to 80% of the GET: (1) during normoxia (NORMO), and (2) during acute, normobaric hypoxia at 13.5% inspired oxygen (HYPO). During the last 3 min of the exercise, they also performed a mental task (MT). Hemodynamics were assessed with impedance cardiography, and peripheral arterial oxygen saturation and Cox were continuously measured by near-infrared spectroscopy. The main results were that both in NORMO and HYPO conditions, the MT caused a significant increase in the heart rate and ventricular filling rate. Moreover, MT significantly reduced (74.8 ± 5.5 vs. 62.0 ± 5.2 A.U.) Cox, while the reaction time (RT) increased (813.3 ± 110.2 vs. 868.2 ± 118.1 ms) during the HYPO test without affecting the correctness of the answers. We conclude that in young, healthy males, adding an MT during mild intensity exercise in both normoxia and acute moderate (normobaric) hypoxia induces a similar hemodynamic response. However, MT and exercise in HYPO cause a decrease in Cox and an impairment in RT. [ABSTRACT FROM AUTHOR]

Background: When inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays a crucial role in the biological behaviour and differentiation of the cells. Recently, flavonoids are increasingly recognized for their therapeutic potential in modulating inflammation and osteogenic differentiation. Owing to their varied molecular structures and mechanisms, there are more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored for both soft and hard tissues was developed to screen for flavonoids suitable for treating periodontitis. Methods: This study developed a microfluidic system that bionically simulates the soft and hard structures of periodontal tissues. Live/dead staining, reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. These techniques evaluated the effects of flavonoid compounds on the levels of inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. Additionally, the impact of these compounds on osteogenic induction in HBMSC and the exploration of the underlying mechanisms were assessed. Results: The microfluidic chip used in this study features dual chambers separated by a porous membrane, allowing cellular signal communication via bioactive factors secreted by cells in both layers under perfusion. The inflammatory response within the chip under LPS stimulation was lower compared to individual static cultures of HGF and HBMSC. The selected flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular inflammation, decreased ROS levels, and enhanced osteogenic differentiation of BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated favorable outcomes in reducing inflammation, lowering ROS levels, and promoting osteogenic differentiation through the Wnt/β-catenin pathway. Conclusions: The bionic microfluidic chip system provides enhanced capabilities for drug screening and evaluation, delivering a more precise assessment of drug efficacy and safety compared to traditional in vitro methods. This study demonstrates the efficacy of flavonoids in influencing osteogenic processes in BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the potential of flavonoids as therapeutic medicine for treating periodontitis, meriting further research and development. [ABSTRACT FROM AUTHOR]

Background: Mn2+-mediated chemodynamic therapy (CDT) has been emerged as a promising cancer therapeutic modality that relies heavily on HCO3− level in the system. Although the physiological buffers (H2CO3/HCO3−) provide certain amounts of HCO3−, the acidity of the tumor microenvironment (TME) would seriously affect the HCO3− ionic equilibrium (H2CO3 ⇌ H+ + HCO3−). As a result, HCO3− level in the tumor region is actually insufficient to support effective Mn2+-mediated CDT. Results: In this study, a robust nanomodulator MnFe2O4@ZIF-8 (PrSMZ) with the capability of in situ self-regulation HCO3− is presented to enhance therapeutic efficacy of Mn2+-mediated CDT. Under an acidic tumor microenvironment, PrSMZ could act as a proton sponge to shift the HCO3− ionic equilibrium to the positive direction, significantly boosting the generation of the HCO3−. Most importantly, such HCO3− supply capacity of PrSMZ could be finely modulated by its ZIF-8 shell thickness, resulting in a 1000-fold increase in reactive oxygen species (ROS) generation. Enhanced ROS-dependent CDT efficacy is further amplified by a glutathione (GSH)-depletion ability and the photothermal effect inherited from the inner core MnFe2O4 of PrSMZ to exert the remarkable antitumor effect on mouse models. Conclusions: This work addresses the challenge of insufficient HCO3− in the TME for Mn2+-mediated Fenton catalysts and could provide a promising strategy for designing high-performance Mn2+-mediated CDT agents to treat cancer effectively. [ABSTRACT FROM AUTHOR]

SUMMARY: Canker disease caused by the bacterium Lonsdalea populi is one of the most destructive diseases affecting poplar stems. However, the detailed stress response mechanisms of poplar have not been widely characterized. To explore the diverse regulatory RNA landscape and the function of key regulators in poplar subjected to L. populi stress, we integrated time‐course experiment with mock‐inoculation (CK) and inoculation (IN) with L. populi at the first, third, and sixth day (IN1, IN3, IN6) on Populus × euramericana cv. '74/76' (107), small RNA‐seq, whole transcriptome‐wide analysis, degradome analysis and transgenic experiments. A total of 98 differentially expressed (DE) miRNA, 17 974 DEmRNA, and 807 DElncRNA were identified in poplar infected by L. populi, presenting dynamic changes over the infection course. Regulatory networks among RNAs were further constructed. Notably, a network centered on ptc‐miR482a in CK‐vs‐IN3 contained most DEGs. We show that miR482a and miR1448 are located in one transcript as a polycistron. Overexpression of pre‐miR482a‐miR1448 (OX482‐1448) and pre‐miR482a (OX482) increased poplar susceptibility to canker pathogen with reduced accumulation of reactive oxygen species, while the suppression of miR482a (STTM482) conferred poplar disease resistance. PHA7 was validated as the target of miR482a with degradome sequencing and tobacco transient co‐transformation, its expression being downregulated in OX482‐1448 and OX482 lines. Additionally, a series of phasiRNAs were triggered by miR482a targeting PHA7, forming regulatory cascades with more RLP, NBS‐LRR, and PK genes, further verifying the defense function of miR482a. These findings provide insights for understanding the roles of ncRNAs and regulatory networks involved in poplar immunity. Significance Statement: This study integrated whole transcriptome‐wide analysis of time‐course inoculation on poplar and identified a center ptc‐miR482a, which is located in one transcript with miR1448 as a polycistron. MiR482a overexpression increased poplar susceptibility to canker pathogen and a series of phasiRNAs were triggered by miR482a targeting PHA7. This work provides insights for understanding the regulatory roles of ncRNAs involved in poplar immunity. [ABSTRACT FROM AUTHOR]

In the last years, the research on the sweet wormwood (Artemisia annua L.) has increasingly become the focus of oncology science. The bioactive ingredient of the plant is artemisinin, which has been proven to be effective in the treatment of malaria. At the same time, Hungarian and international research groups are also investigating the plant, with the research aimed at the treatment of malignant cancer. In Europe, the therapeutic use of medicinal plants against tumours is realized in relatively few countries, in contrast, phytotherapy research in Asia reports results with a significant therapeutic effect. The aim of our work was to investigate the antioxidant effect of Artemisia annua. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Oxygen radical absorbance capacity (ORAC) laboratory assays proved that the parts of the herb show a significant antioxidant effect, while the seed and the extracted bioactive ingredient artemisinin have no antioxidant capacity at all. On the other hand, aqueous extracts made from leafy shoots showed promising antioxidant capacity values DPPH 10.48 ±0.46. Due to its bitter taste index 1548, it can be used in premixed feed e.g. for piglets. [ABSTRACT FROM AUTHOR]

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of the tyrosine degradation pathway. In this study, we isolated and characterized two homologous BnaFAH genes in Brassica napus L. variant Westar, and then used CRISPR/Cas9-mediated targeted mutagenesis to generate a series of transgene-free mutant lines either with single or double-null bnafah alleles. Among these mutant lines, the aacc (bnafah) double-null mutant line, rather than the aaCC (bnaa06fah) mutant line, exhibited programmed cell death (PCD) under short days (SD). Histochemical staining and content measurement confirmed that the accumulation of reactive oxygen species (ROS) in bnafah was significantly higher than that in bnaa06fah. To further elucidate the mechanism of PCD, we performed transcriptomic analyses of bnaa06fah and bnafah at different SD stages. A heatmap cluster of differentially expressed genes (DEGs) revealed that PCD may be related to various redox regulatory genes involved in antioxidant activity, ROS-responsive regulation and calcium signaling. Combined with the results of previous studies, our work revealed that the expression levels of BnaC04CAT2, BnaA09/C09SAL1, BnaA08/C08ACO2, BnaA07/C06ERO1, BnaA08ACA1, BnaC04BIK1, BnaA09CRK36 and BnaA03CPK4 were significantly different and that these genes might be candidate hub genes for PCD. Together, our results underscore the ability of different PCD phenotypes to alter BnaFAH orthologs through gene editing and further elucidated the molecular mechanisms of oxidative stress-induced PCD in plants. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a major disease characterized by early albuminuria and heightened risk of renal deterioration. Increased reactive oxygen species (ROS) production, especially in glomeruli, plays an important role in the progression of DKD. ROS also cause activation of Apoptosis signal-regulating kinase 1 (ASK-1), which is implicated in various organ injuries. However, the detailed mechanisms remain unclear. This study investigates ASK-1 activation in advanced DKD and its underlying mechanisms using GS442172, an ASK-1 inhibitor. In the DKD mouse model, activation of ASK-1 was observed. Although inhibition of ASK-1 activation improved hyperpermeability in glomerular endothelial cells. ASK-1 inhibition significantly reduced glomerular injury and albuminuria, while also attenuating tubular damage and interstitial fibrosis. RNA-seq analysis revealed an aging phenotype associated with ASK-1 activation in DKD. In vitro experiments demonstrated ASK-1 activation-induced cellular senescence in tubular cells via redox signaling. These results suggested that the critical role of ASK-1 activation in DKD pathogenesis, implicating glomerular injury, tubular damage, and cellular senescence. ASK-1 inhibitors are promising therapeutic strategies to mitigate the progression of DKD. [ABSTRACT FROM AUTHOR]

Low temperatures are a key factor affecting the growth, development, and geographical distribution of prickly ash. This study investigated the impact of ecological and geographical factors on the freezing tolerance of prickly ash germplasm. Thirty-seven germplasm samples from 18 different origins were collected, and their freezing tolerance was comprehensively evaluated. The correlation between freezing tolerance and the ecological and geographical factors of their origins was also analyzed. Significant differences in freezing tolerance were observed among germplasm from different origins. The semi-lethal temperature of the germplasm ranged from − 12.37 to 1.08 °C. As temperatures decreased, the relative conductivity (REC) and catalase (CAT) activity of the germplasm gradually increased, while soluble sugar (SS), soluble protein (SP), free proline (Pro), and Peroxidase (POD) activities decreased and then increased. Superoxide dismutase (SOD) activity initially increased and then decreased. A comprehensive evaluation of freezing tolerance was conducted using a logistic equation, membership function, and cluster analysis. Germplasm from Tongchuan and Hancheng (Shaanxi Province, China), Asakura (Japan), and Yuncheng (Shanxi Province, China) exhibited the highest freezing tolerance, whereas those from Rongchang (Chongqing Municipality, China), Qujing (Yunnan Province, China), and Honghe (Yunnan Province, China) had the lowest. The correlation analysis revealed a significant positive correlation between freezing tolerance and latitude, and a significant negative correlation with the temperature of origin. Germplasm from higher latitudes showed higher SS content, SOD and CAT activities, stronger antioxidant enzyme activity, and better freezing tolerance compared to those from lower latitudes. REC was lower in germplasm originating from low-temperature areas than in those from high-temperature areas. Additionally, SP, Pro content, SOD, and POD activities were higher, indicating effective scavenging of active oxygen free radicals. No significant correlation was found between altitude and longitude of origin and freezing tolerance. However, at similar latitudes, prickly ash from higher altitudes displayed higher antioxidant enzyme activity and stronger freezing tolerance compared to those from lower altitudes. These findings provide a scientific basis for breeding prickly ash cultivars suited to different ecological regions. [ABSTRACT FROM AUTHOR]

Organic photosensitizers (PSs) can generate reactive oxygen species (ROS) via electron transfer (type I) and energy transfer (type II) pathways during photodynamic therapy (PDT). However, although numerous organic PSs have been constructed, the methods to optimize both type I and type II ROS generation are still not well explored. In this work, molecular engineering is applied to design three new organic PSs with varying triplet lifetimes and intersystem crossing (ISC) efficiency to achieve highly efficient type I&II ROS generation. The results reveal that after coated into nanoparticles (NPs) with DSPE‐PEG2000‐Biotin, the PS of mBDP‐PyH with the longest triplet lifetime and moderate ISC efficiency possesses good type II ROS and moderate type I ROS generation. With other properties being similar, the PS of mBDP‐2Py exhibits a shorter triplet lifetime, accompanied by concurrently reduced ROS generation for both types inside NPs. In contrast, the most potent PS of mBDP‐PyBr exhibits the shortest triplet lifetime but highly efficient ISC, with its NPs showing superior type I&II ROS generation. Moreover, both in vitro and in vivo experiments indicate that mBDP‐PyBr NPs display outstanding light toxicity under normoxic and hypoxic conditions. Overall, this study provides valuable guidance in designing effective organic PSs for PDT. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injuries (TBIs) are one of the leading causes of death or long‐term disability around the world. As a result of improvements in supportive care, patients are surviving more severe insults with more pronounced dependency on their families, hospitals, and long‐term care facilities. The introduction of brain tissue oxygenation (PbtO2) monitoring aims to recognize episodes of reduced cerebral perfusion with and without associated increased intracranial pressure (ICP). Aim: The aim of this review is to determine the impact of PbtO2 on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended (GOS/GOSE) in patients with moderate to severe TBI. Study Design: Systematic review with narrative and meta‐analysis. All original research in which adult patients undergoing PbtO2 were compared with a control group of traditional ICP/cerebral perfusion pressure (CPP) monitoring. Both randomized controlled trials and observational studies were included in this review. Methods: Databases were searched in September 2022. The primary outcome of the review was the impact of PbtO2 monitoring on GOS/GOSE, while secondary outcomes were mortality and length of stay (LOS) in the intensive care unit (ICU). Results: Seven studies with a combined number of 770 patients were included in the review. These patients were adults ≥16 years of age. Only two of the studies included found a statistically significant association between PbtO2 monitoring and improved long‐term neurological outcomes in patients with TBI (p =.01, p <.01). A meta‐analysis of the secondary outcomes identified an associated reduction of mortality in favour of the group treated with PbtO2 monitoring (p <.0001). Results from studies examining LOS in ICU have demonstrated an associated increase of LOS in ICU in patients treated with PbtO2‐guided therapy. Conclusion: From the studies included in this review, only two found a statistically significant association between PbtO2 monitoring and long‐term outcomes. It is unclear whether PbtO2 goal‐directed therapy has a positive impact on the long‐term neurological functions and mortality of patients suffering from TBI. A multicentre randomized controlled trial may provide further evidence, but not necessarily conclusive. Relevance to Clinical Practice: Further research is warranted to determine the efficacy of the introduction of this new monitoring system to guide local policy change. [ABSTRACT FROM AUTHOR]

Summary Heat stress (HS) has become a major factor limiting crop yields worldwide. HS inhibits plant growth by ROS accumulation, and NADPH oxidases (Rbohs) are major ROS producers in plants. Here, we show that CRISPR/Cas knockout of the OsRbohB (OsRbohB‐KO) significantly increased rice tolerance to HS imposed at various different growth stages. We produced OsRbohB‐KO and OsRbohB‐overexpression (OsRbohB‐OE) lines in a japonica cultivar, Nipponbare. Compared with nontransgenic wild‐type (WT) plants, the OsRbohB‐KO lines showed a significant increase in chlorophyll contents (5.2%–58.0%), plant growth (48.2%–65.6%) and grain yield (8.9%–20.5%), while reducing HS‐induced ROS accumulation in seeds (21.3%–33.0%), seedlings (13.0%–30.4%), anthers (13.1%–20.3%) and grains (9.7%–22.1%), under HS conditions. Analysis of yield components revealed that the increased yield of OsRbohB‐KO plants was due to increased starch synthetase activity, spikelets per panicle (2.0%–9.3%), filled spikelets (4.8%–15.5%), percentage of filled spikelets (2.4%–6.8%) and 1000‐grain weight (2.9%–7.4%) under HS conditions during the reproductive stage. Grain milling and appearance quality, and starch content were also significantly increased in OsRbohB‐KO plants under HS conditions during the mature stage. Furthermore, OsRbohB‐KO significantly upregulated the expression levels of heat shock‐related genes, OsHSP23.7, OsHSP17.7, OsHSF7 and OsHsfA2a, in rice seedlings and grains under long‐term HS conditions. Conversely, OsRbohB‐OE resulted in phenotypes that were opposite to OsRbohB‐KO in most cases. Our results suggest that suppression of OsRbohB provides an effective approach for alleviating heat damage and improving grain yield and quality of rice under long‐term HS conditions. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION The black goji berry (Lycium ruthenicum Murr.) is known for its abundance of high‐quality natural antioxidants, particularly anthocyanins. Black goji berry anthocyanins (BGA) are receiving increasing attention because of their high safety and beneficial biological activities. Studies have shown that oxidative stress is a key factor affecting aging, whereas antioxidants are critical preventive and delaying strategies.In the present study, we investigated the potential anti‐aging effects and mechanism of BGA using the Caenorhabditis elegans model. We found that BGA prolonged the mean lifespan of nematodes and improve their healthspan, including locomotion, pharyngeal pumping rate and stress resistance. Subsequently, we observed a significant decrease in reactive oxygen species and malondialdehyde levels in nematodes after administering BGA. Moreover, BGA enhanced the activities of the antioxidant enzymes superoxide dismutase and catalase, and elevated the glutathione disulfide/glutathione ratio. We confirmed that BGA exerted excellent antioxidative stress activity in nematodes, which may contribute substantially to its anti‐aging effects. The health benefits of BGA in C. elegans might be closely related to petunidin‐3‐O‐glucoside, the most abundant anthocyanin in BGA. Further mechanistic investigation revealed that the JNK‐1 and DAF‐16/FOXO pathways, rather than the calorie restriction pathway, were responsible for the antioxidant stress and life‐prolonging effects of BGA in nematodes.Our research provides a theoretical foundation for studying the anti‐aging effect of BGA and a basis for developing black goji berry and its anthocyanins as functional foods with anti‐aging and antioxidative stress benefits. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The primary goals of this study were to investigate the formation of abasic sites (AP sites) induced by methyl methanesulfonate (MMS) and hydrogen peroxide (H 2 O 2), and to characterize specific types of these pro-mutagenic DNA lesions in calf thymus DNA (CT-DNA), and BEAS-2B human lung normal cell line. Furthermore, these profiles were compared with those observed in leukocytes derived from healthy controls (HC), breast cancer patients (BCP) before treatment, and 5-year survivors. Results indicated that both H 2 O 2 and MMS induced the concentration- and time-dependent formation of AP sites in CT-DNA. To characterize the specific types of AP sites induced by H 2 O 2 or MMS, we performed AP site cleavage assay using putrescine, T7 exonuclease (T7 Exo), and exonuclease III (Exo III). Results showed that the AP sites induced by H 2 O 2 in CT-DNA were predominantly 5'-and 3'-nicked AP sites and no intact AP sites were detected. By contrast, the majority of AP sites generated by MMS in CT-DNA are not excisable and are classified as residual and intact AP sites. Similar approaches were performed in human BEAS-2B cells and comparable observations were confirmed in the cell-based model. Further investigation indicated that the profile of the AP sites observed in Taiwanese HC is identical to that of BEAS-2B cells treated with H 2 O 2 whereas the pattern of AP sites detected in BCP is similar to that of CT-DNA exposed to H 2 O 2 , suggesting that these AP sites were produced primarily through reactive oxygen species (ROS) generation. More than 70 % of the AP sites in leukocytes derived from BCP were 5'-nicked and residual AP sites. Furthermore, the characteristics of the AP sites detected in 5-year survivors are comparable with the ones in HC by using putrescine cleavage assay. Overall, we speculate that deficiency in the DNA repair cascade may play a role in mediating the formation of specific types of AP sites detected in BCP. [Display omitted] • H 2 O 2 predominantly induces 5'-cleaved AP sites. • MMS predominantly induces non-excisable AP sites. • The profile of AP sites in leukocytes of healthy controls is similar to that of BEAS-2B cells treated with H 2 O 2. • The profile of AP sites in leukocytes of breast cancer patients is similar to that of CT-DNA exposed to H 2 O 2. • The predominant AP sites in human leukocytes are derived from oxidative stress primarily through the generation of ROS. [ABSTRACT FROM AUTHOR]

Melanin, particularly eumelanin, is commonly viewed as an efficient antioxidant and photoprotective pigment. Nonetheless, the ability of melanin to photogenerate reactive oxygen species and sensitize the formation of cyclobutane pyrimidine dimers may contribute to melanin‐dependent phototoxicity. The phototoxic potential of melanin depends on a variety of factors, including molecular composition, redox state, and degree of aggregation. Using complementary spectroscopic and analytical methods we analyzed the physicochemical properties of Dopa‐melanin, a synthetic model of eumelanin, subjected to oxidative degradation induced by aerobic photolysis or exposure to 0.1 M hydrogen peroxide. Both modes of oxidative degradation were accompanied by dose‐dependent bleaching of melanin and irreversible modifications of its paramagnetic, ion‐ and electron‐exchange and antioxidant properties. Bleached melanin exhibited enhanced efficiency to photogenerate singlet oxygen in both UVA and short‐wavelength visible light. Although chemical changes of melanin subunits, including a relative increase of DHICA content and disruption of melanin polymer induced by oxidative degradation were considered, these two mechanisms may not be sufficient for a satisfactory explanation of the elevated photosensitizing ability of the bleached eumelanin. This study points out possible adverse changes in the photoprotective and antioxidant properties of eumelanin that could occur in pigmented tissues after exposure to high doses of intense solar radiation. [ABSTRACT FROM AUTHOR]

In order to meet growing consumer demands in terms of naturalness, the pharmaceutical, food, and cosmetic industries are looking for active molecules of plant origin. In this context, hairy roots are considered a promising biotechnological system for the sustainable production of compounds of interest. Poplars (genus Populus, family Salicaceae) are trees of ecological interest in temperate alluvial forests and are also cultivated for their industrial timber. Poplar trees also produce specialized metabolites with a wide range of bioactive properties. The present study aimed to assess the hybrid poplar hairy root extracts for antimicrobial and antibiofilm activities against four main life-threatening strains of Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Ethyl acetate extracts from two hairy root lines (HP15-3 and HP A4-12) showed significant antibacterial properties as confirmed by disc diffusion assay. Antibiofilm activities were found to be dose dependent with significant biofilm inhibition (75–95%) recorded at 1000 µg.mL−1 in all the bacterial strains tested. Dose-dependent enhancement in the release of exopolysaccharides was observed in response to treatment with extracts, possibly because of stress and bacterial cell death. Fluorescence microscopy confirmed loss of cell viability of treated bacterial cells concomitant with increased production of reactive oxygen species compared to the untreated control. Overall, this study demonstrates for the first time a high potential of poplar hairy root extracts as a natural and safe platform to produce antimicrobial agents in pharmaceutical, food, industrial water management, or cosmetic industries. [ABSTRACT FROM AUTHOR]

Purpose: Lycium barbarum polysaccharides (LBPs) have been proven to protect the eyes by inhibiting apoptosis. This study was designed to investigate the effect of LBPs on DNA damage and oxidative stress induced by ultraviolet B (UVB) radiation in human corneal epithelial cells (HCECs). Methods: HCECs were divided into a control group, UVB group and UVB + LBP group and treated with varying concentrations of LBP (0, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6 and 3.2 mg/mL). Then, the effects of LBP on the viability and apoptosis of HCECs were detected via MTT assay and flow cytometry. Additionally, the contents of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) in the cells of each group were measured to evaluate the level of oxidative stress. Results: LBP at a concentration of 0.4 mg/mL showed the best effect on promoting the viability and inhibiting the apoptosis of HCECs. Compared with the control group, the UVB and UVB + LBP groups exhibited significantly decreased levels of cell viability and SOD and notably increased apoptosis, MDA, ROS, tail DNA percentage, olive tail moment, p-CHK2, and gamma histone (γH2AX). In contrast to the UVB group, the UVB + LBP group presented notably upregulated levels of cell viability and SOD and downregulated apoptosis, MDA, ROS, tail DNA percentage, olive tail moment, p-CHK2, and γH2AX. Conclusions: The optimal concentration of LBP to promote the viability and reduce the apoptosis of HCECs is 0.4 mg/mL. Moreover, LBP can alleviate DNA damage and oxidative stress induced by UVB in HCECs. [ABSTRACT FROM AUTHOR]