Reactive Oxygen Species Balance Research Articles

Assessing the Effect of Cold Plasma on the Softening of Postharvest Blueberries through Reactive Oxygen Species Metabolism Using Transcriptomic Analysis.

The postharvest softening and corresponding quality deterioration of blueberry fruits are crucial factors that hinder long-distance sales and long-term storage. Cold plasma (CP) is an effective technology to solve this, but the specific mechanism of delaying fruit softening remains to be revealed. Here, this study found that CP significantly improved blueberry hardness. Physiological analysis showed that CP regulated the dynamic balance of reactive oxygen species (ROS) to maintain hardness by increasing antioxidant content and antioxidant enzyme activity, resulting in a 12.1% decrease in the H2O2 content. Transcriptome analysis revealed that CP inhibited the expression of cell wall degradation-related genes such as the pectin hydrolase gene and cellulase gene, but up-regulated the genes of the ROS-scavenging system. In addition, the resistance genes in the MAPK signaling pathway were also activated by CP in response to fruit ripening and softening and exhibited positive response characteristics. These results indicate that CP can effectively regulate the physiological characteristics of blueberries at a genetic level and delay the softening process, which is of great significance to the storage of blueberries.

Exploring the Therapeutic Potential of Flavonoids in the Management of Cancer.

Flavonoids are a class of polyphenolic compounds that can be classified into six distinct categories, namely isoflavonoids, flavanones, flavanols, flavonols, flavones, and anthocyanidins. These compounds are naturally occurring and can be found in a diverse range of plant species. Flavonoids, a class of bioactive compounds, are mostly obtained through the consumption of vegetables, fruits and plant-derived beverages such as wine, cocoa-based products and green tea. Flavonoids have been demonstrated to exhibit a diverse range of anticancer properties. These include the modulation of activities of enzymes involved in scavenging reactive oxygen species, involvement in cell cycle arrest, induction of apoptosis and autophagy, as well as suppression of cancer cell proliferation and invasiveness. Flavonoids exhibit a dual role in maintaining reactive oxygen species balance. They function as antioxidants in regular physiological conditions, while also demonstrating significant pro-oxidant properties in cancer cells. This prooxidant activity induces apoptotic pathways and downregulates pro-inflammatory signalling pathways. The paper explores the biochemical characteristics, bioavailability, anticancer efficacy, and modes of action of flavonoids.

Cu-II-directed self-assembly of fullerenols to ameliorate copper stress in maize seedlings

Widespread use of copper-based agrochemical may cause copper excessive accumulation in agricultural soil to seriously threaten crop production. Recently, fullerenols are playing important roles in helping crops build resistance to abiotic stresses by giving ingenious and successful resolutions. However, there is a lack of knowledge on their beneficial effects in crops under stresses induced by heavy metals. Herein, the visual observation of Cu2+-mediated assembly of fullerenols via electrostatic and coordination actions was carried out in vitro, showing that water-soluble nanocomplexes and water-insoluble cross-linking nanohybrids were selectively fabricated by precisely adjusting feeding ratios of fullerenols and CuSO4. Furthermore, maize simultaneous exposure of fullerenols and CuSO4 solutions was tested to investigate the comparative effects of seed germination and seedling growth relative to exposure of CuSO4 alone. Under moderate Cu2+ stresses (40 and 80 μM), fullerenols significantly mitigated the detrimental effects of seedlings, including phenotype, root and shoot elongation, biomass accumulation, antioxidant capacity, and Cu2+ uptake and copper transporter-related gene expressions in roots. Under 160 μM of Cu2+ as a stressor, fullerenols also accelerated germination of Cu2+-stressed seeds eventually up to the level of the control. Summarily, fullerenols can enhance tolerance of Cu2+-stressed maize mainly due to direct detoxification through fullerenol-Cu2+ interactions restraining the Cu2+ intake into roots and reducing free Cu2+ content in vivo, as well as fullerenol-maize interactions to enhance resistance by maintaining balance of reactive oxygen species and optimizing the excretion and transport of Cu2+. This will unveil valuable insights into the beneficial roles of fullerenols and its mechanism mode in alleviating heavy metal stress on crop plants.

Mitigation of ROS-triggered endoplasmic reticulum stress by upregulating Nrf2 retards diabetic nephropathy

Endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of diabetic nephropathy (DN), and it is often accompanied by an increase in reactive oxygen species (ROS) production. However, the precise relationship between nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of ROS balance, and ERS in DN remains elusive. This study aimed to investigate the impact of Nrf2 on ERS and its therapeutic potential in DN. Herein, ERS-related changes, including increased activating transcription factor-6 (ATF6), glucose-regulated protein 78 (GRP78), and transcription factor C/EBP homologous protein (CHOP) expression, were observed in the renal tissues of streptozotocin-induced DN mice and high glucose cultured human renal proximal tubular (HK-2) cells. Nrf2 knockdown increased the sensitivity of HK-2 cells to ERS under high glucose conditions, underscoring the regulatory role of Nrf2 in ERS modulation. Notably, upregulating Nrf2 in ezetimibe-treated diabetic mice restored ERS markers and ameliorated albuminuria, glomerular hypertrophy, mesangial expansion, and tubulointerstitial fibrosis. Furthermore, the inhibition of ERS in HK-2 cells by the ROS scavenger, N-acetylcysteine, highlights the interplay between ROS and ERS. This study, for the first time, elucidates that the upregulation of Nrf2 may alleviate the negative influence of ROS-mediated ERS, presenting a promising therapeutic avenue for delaying the progression of DN. These findings suggest a potential strategy for targeting Nrf2 and ERS in developing novel therapeutic interventions for DN.

Proline-rich protein PRPL1 enhances Panax notoginseng defence against Fusarium solani by regulating reactive oxygen species balance and strengthening the cell wall barrier.

The root rot mainly caused by Fusarium solaniis a bottleneck in the cultivation of Panax notoginseng. In this study, we reported a gene encoding a plant cell wall structural protein, P. notoginseng proline-rich protein (PnPRPL1), whose transcription was upregulated by F. solani and induced by some hormone signals. The PnPRPL1 recombinant protein significantly inhibited the growth and conidial germination of the root rot pathogens. Downregulation of PnPRPL1 byRNA interference(RNAi) in P. notoginseng leaves increased the susceptibility to F. solani, whereas overexpression of PnPRPL1 in tobacco (Nicotiana tabacum) enhanced the resistance to F. solani. Compared with wild-type tobacco, the PnPRPL1-overexpressing transgenic tobacco had higher reactive oxygen species (ROS)-scavenging enzyme activities, lower ROS levels, and more lignin and callose deposition. The opposite results were obtained for the P. notoginseng expressing PnPRPL1 RNAi fragments. Furthermore, the PnPRPL1 promoter transcription activity was induced by several plant hormones and multiple stress stimuli. In addition, the transcription factor PnWRKY27 activated the expression of PnPRPL1 by directly binding to the promoter region. Thus, PnPRPL1, which is positively regulated by a WRKY transcription factor, encodes an antimicrobial protein that also mediates ROS homoeostasis and callose/lignin deposition during the response to F. solani infection.

ROS Balance Autoregulating Core–Shell CeO2@ZIF-8/Au Nanoplatform for Wound Repair

HighlightsThe innovation of this work mainly lies in the auto-regulation of reactive oxygen species (ROS) balance effective by combination of ROS antibacterial and ROS scavenging anti-inflammatory functions with a core–shell nanoplatform (CeO2@ZIF-8/Au), which can not only achieve high antibacterial efficiency, but also promote wound healing, and provide a new idea for the nano-catalytic system in the field of wound healing of bacterial infection.

Analysis of the Effects of Pentose Phosphate Pathway Inhibition on the Generation of Reactive Oxygen Species and Epileptiform Activity in Hippocampal Slices.

The pentose phosphate pathway (PPP) is one of three major pathways involved in glucose metabolism, which is regulated by glucose-6-phosphate dehydrogenase (G6PD) controls NADPH formation. NADPH, in turn, regulates the balance of oxidative stress and reactive oxygen species (ROS) levels. G6PD dysfunction, affecting the PPP, is implicated in neurological disorders, including epilepsy. However, PPP's role in epileptogenesis and ROS production during epileptic activity remains unclear. To clarify these points, we conducted electrophysiological and imaging analyses on mouse hippocampal brain slices. Using the specific G6PD inhibitor G6PDi-1, we assessed its effects on mouse hippocampal slices, examining intracellular ROS, glucose/oxygen consumption, the NAD(P)H level and ROS production during synaptic stimulation and in the 4AP epilepsy model. G6PDi-1 increased basal intracellular ROS levels and reduced synaptically induced glucose consumption but had no impact on baselevel of NAD(P)H and ROS production from synaptic stimulation. In the 4AP model, G6PDi-1 did not significantly alter spontaneous seizure frequency or H2O2 release amplitude but increased the frequency and peak amplitude of interictal events. These findings suggest that short-term PPP inhibition has a minimal impact on synaptic circuit activity.

Physiological and transcriptomic analysis of Hordeum jubatum seedlings in response to salt, alkali and drought stresses under uniform water potential

The early seedling stage is highly susceptible to various abiotic stresses. Hordeum jubatum is an ornamental plant with excellent abiotic stress tolerance, and widely distributed in the northeast of China. However, the mechanism of its physiological and transcriptional resistance under different abiotic stresses is still unclear. The results showed that the leaves of H. jubatum adapted to saline-alkali and drought environments by increasing the density of wax and glandular hairs, reducing the stomatal length, width and opening, and the leaf cells completely ruptured and a large number of organelles disintegrated under alkali stress. With the increasing stress concentration, the chlorophyll content and dry weight reduced under the three stresses, which was related to the broken chloroplasts of such conditions. In addition, the balance of Na+ and K+ was disturbed, and the increase of APX and SOD activity was the strategy to maintain the balance of reactive oxygen species and weaken the degree of membrane lipid peroxidation under three stresses. And alkali stress had the most significant effect on above changes. Moreover, Transcriptional sequencing revealed the alkali stress group had the highest number of differential expressed genes (DEGs) compared to the CK among three stresses, and a significant down-regulation of DEGs related to membrane systems under three stresses. In addition, alkali stress resulted in large number of up-regulation of DEGs associated with light repair processes and down-regulation of DEGs in ribosomal pathway with R proteins involving in regulating leaf phenotype and ultrastructure, which also echoed the overall physiological findings. Together, the adaptation mechanisms of three stresses were different in H. jubatum seedlings with higher tolerance of salt stress, and extremely sensibility to alkali stress.

Oxidase enzyme genes are differentially expressed during Acanthamoeba castellanii encystment.

Acanthamoeba castellanii, a ubiquitous protozoan, is responsible for significant diseases such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. A crucial survival strategy of A. castellanii involves the formation of highly resistant cysts during adverse conditions. This study delves into the cellular processes underpinning encystment, focusing on gene expression changes related to reactive oxygen species (ROS) balance, with a particular emphasis on mitochondrial processes. Our findings reveal a dynamic response within the mitochondria during encystment, with the downregulation of key enzymes involved in oxidative phosphorylation (COX, AOX, and NADHalt) during the initial 48h, followed by their overexpression at 72h. This orchestrated response likely creates a pro-oxidative environment, facilitating encystment. Analysis of other ROS processing enzymes across the cell reveals differential expression patterns. Notably, antioxidant enzymes, such as catalases, glutaredoxins, glutathione S-transferases, peroxiredoxins, and thioredoxins, mirror the mitochondrial trend of downregulation followed by upregulation. Additionally, glycolysis and gluconeogenesis are downregulated during the early stages in order to potentially balance the metabolic requirement of the cyst. Our study underscores the importance of ROS regulation in Acanthamoeba encystment. Understanding these mechanisms offers insights into infection control and identifies potential therapeutic targets. This work contributes to unraveling the complex biology of A. castellanii and may aid in combatting Acanthamoeba-related infections. Further research into ROS and oxidase enzymes is warranted, given the organism's remarkable respiratory versatility.

Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP, and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.

Nitric oxide delays the postharvest nutritional quality decline of “Golden Hook” beans

Abstract“Golden Hook” beans turn purple to different degrees due to the different compositions and contents of flavonoids during storage. At the same time, quality losses due to softening or pathogen invasion, and the deteriorations of flavor associated with carbohydrate metabolism occur. To reveal the effect of nitric oxide (NO) generated from sodium nitroprusside (SNP) on the postharvest quality of “Golden Hook” beans, we used metabolome, transcriptome, and assay for transposase‐accessible chromatin with high‐throughput sequencing approaches to compare beans at the time of treatment with untreated and SNP‐treated beans stored at 8°C for 12 days. The results showed that NO induced the expression of CERK1, FLS2, JAZ, and MYC2, stimulated the expression of polyphenol oxidase, CAT, and l‐ascorbate oxidase, the accumulation of flavonoids, and the synthesis of lignin in the antioxidant system, improving the ability of beans to resist stress while maintaining the balance of reactive oxygen species. High expressions of F3′H, FLS, INV, SUS, BCAT, and the accumulation of 6‐C‐methylquercetin‐3‐O‐rutinoside were associated with the maintenance of the fresh purplish red appearance of the beans in the SNP‐12d group, without loss of flavor. SNP treatment downregulated the transcription factors blimp‐1, OBP1, COG1, and AT1G6957 associated with bean senescence. These results provide insight into the postharvest quality control of “Golden Hook” beans.

Utilization of ovalbumin and visible light irradiation for efficient and eco‐friendly production of AgNPs composite

Silver nanoparticles (AgNPs) are one of the most widely used antimicrobial agents. However, due to the potential problems of environmental pollution and high energy consumption, a green and efficient synthesis strategy of AgNPs is urgently required. Ovalbumin (OVA) is the most abundant protein in egg whites, and its extraction process is simple and productive. This paper reported a new green synthesis method of AgNPs by using OVA as an assistant accompanying with a visible light irradiation. Together with the reduction of silver ions, the uniformly dispersed OVA‐AgNPs nanocomposite could be formed within 30 min under xenon light irradiation by simple mixing AgNO3 and OVA in aqueous solution. The detailed mechanism study showed that tyrosine residue and peptide bonds in OVA played a major role in the reduction and stability of silver ions. In addition, in vitro antibacterial experiments indicated that 10 mg/L of OVA‐AgNPs, the minimum inhibitory concentration, has a good antimicrobial effect on both Gram‐positive and Gram‐negative bacteria, fungi, and some drug‐resistant bacteria species within 4 h of treatment, mainly due to the disruption of the structure of bacterial cell and the balance of reactive oxygen species. This work provides a new way for the green and efficient synthesis of AgNPs and shows good prospects for the applications in the field of biomedical materials and functional nanomaterials.

ROS scavenging activity of polydopamine nanoparticle-loaded supramolecular gelatin-based hydrogel promoted cardiomyocyte proliferation

Reactive oxygen species (ROS) play essential roles in cellular functions, but maintaining ROS balance is crucial for effective therapeutic interventions, especially during cell therapy. In this study, we synthesized an injectable gelatin-based hydrogel, in which polydopamine nanoparticles were entrapped using supramolecular interactions. The surfaces of the nanoparticles were modified using adamantane, enabling their interactions with β-cyclodextrin-conjugated with gelatin. We evaluated the cytotoxicity and antioxidant properties of the hydrogel on neonatal rat cardiomyocytes (NRCM), where it demonstrated the ability to increase the metabolic activity of NRCMs exposed to hydrogen peroxide (H2O2) after 5 days. Hydrogel-entrapped nanoparticle exhibited a high scavenging capability against hydroxyl radical, 1'-diphenyl-2-picrylhydrazyl radicals, and H2O2, surpassing the effectiveness of ascorbic acid solution. Notably, the presence of polydopamine nanoparticles within the hydrogel promoted the proliferation activity of NRCMs, even in the absence of excessive ROS due to H2O2 treatment. Additionally, when the hydrogel with nanoparticles was injected into an air pouch model, it reduced inflammation and infiltration of immune cells. Notably, the levels of anti-inflammatory factors, IL-10 and IL-4, were significantly increased, while the pro-inflammatory factor TNF-α was suppressed. Therefore, this novel ROS-scavenging hydrogel holds promise for both efficient cell delivery into inflamed tissue and promoting tissue repair.

Identification of new antioxidant drugs in a human in vitro model of ageing‐associated cataract

Aims/Purpose: Cataracts are a significant cause of global blindness, impacting millions (10.8 million patients), and their prevalence is expected to increase over the coming decades as our populations age. Oxidative stress disrupts ROS (reactive oxygen species) balance in lens fibre cells, leading to lens protein degradation and accumulation, developing age‐related cataracts. The lens has protective mechanisms, including high GSH levels and antioxidant enzymes like catalase, safeguarding lens health. While surgery is currently the only effective treatment, non‐invasive drug‐based approaches show potential by reducing risks and complications. With its potent antioxidant activity, resveratrol may protect lens cells and slow cataract development. However, the limited ability of resveratrol to penetrate lens tissue restricts its direct effects. Therefore, designing new molecules to improve ADME (absorption, distribution, metabolism and excretion) properties is required.Methods: In this study, we used an in vitro model of cataracts by inducing oxidative stress and cell death by adding hydrogen peroxide (H2O2) and luperox to lens epithelial cells to evaluate the protective effects of new molecules against oxidative stress and compared them with resveratrol. Our study assessed the cell viability, intracellular ROS level, mitochondrial function, catalase activity and GSH/GSSH level.Results: These compounds preserved cell viability, reduced ROS levels, maintained mitochondrial function and enhanced catalase activity and GSH levels in lens epithelial cells exposed to H2O2. The novel drugs, CAB‐C1 and CAB‐C2, demonstrated beneficial effects on cellular health.Conclusions: Developing drugs for cataract treatment enables early intervention, particularly for individuals with mild or moderate cataracts who may not require surgery yet. Such advancements might improve patients' quality of life and have implications for ocular science and age‐related eye diseases.

REDOX Balance in Oligodendrocytes Is Important for Zebrafish Visual System Regeneration.

Zebrafish (Danio rerio) present continuous growth and regenerate many parts of their body after an injury. Fish oligodendrocytes, microglia and astrocytes support the formation of new connections producing effective regeneration of the central nervous system after a lesion. To understand the role of oligodendrocytes and the signals that mediate regeneration, we use the well-established optic nerve (ON) crush model. We also used sox10 fluorescent transgenic lines to label fully differentiated oligodendrocytes. To quench the effect of reactive oxygen species (ROS), we used the endogenous antioxidant melatonin. Using these tools, we measured ROS production by flow cytometry and explored the regeneration of the optic tectum (OT), the response of oligodendrocytes and their mitochondria by confocal microscopy and Western blot. ROS are produced by oligodendrocytes 3 h after injury and JNK activity is triggered. Concomitantly, there is a decrease in the number of fully differentiated oligodendrocytes in the OT and in their mitochondrial population. By 24 h, oligodendrocytes partially recover. Exposure to melatonin blocks the changes observed in these oligodendrocytes at 3 h and increases their number and their mitochondrial populations after 24 h. Melatonin also blocks JNK upregulation and induces aberrant neuronal differentiation in the OT. In conclusion, a proper balance of ROS is necessary during visual system regeneration and exposure to melatonin has a detrimental impact.

Pre and postharvest spraying of arginine enhanced the stress resistance and promoted wound healing in broccoli during storage

Broccoli rapidly yellows and dehydrates post-harvest, causing a short storage life. Although arginine post-harvest has been shown to enhance broccoli’s storage quality and shelf life, it remains unclear whether pre-harvest treatment yields similar benefits. The results showed that pre-harvest spraying of 5 mM arginine reduces the respiration rate and delays electrolyte leakage during broccoli’s storage period, minimizing weight loss and yellowing and chlorophyll degradation. It also inhibits the degradation of ascorbic acid (ASA) and promotes the synthesis of total phenols, thereby increasing the total antioxidant capacity. Further studies showed that pre-harvest arginine spraying enhanced the activity of arginine decarboxylase (ADC), ornithine decarboxylase (ODC), and nitric oxide synthase (NOS). This accelerated the nitric oxide (NO) and the polyamine (PA) accumulation. Additionally, arginine aids in reactive oxygen species (ROS) balance and wound healing. Notably, pre-harvest arginine spraying was found to inhibit the hydrogen peroxide (H2O2) accumulation and enhance the activities of superoxide dismutase (SOD) and catalase (CAT), while also activating the phenylalanine ammonia lyase (PAL) and cinnamic acid 4-hydroxylase (C4H) activities. In conclusion, pre-harvest arginine spraying extends the broccoli’s storage life and improves its storage quality by promoting endogenous arginine catabolism, ROS metabolism, and the wounds healing. Therefore, this study establishes a theoretical foundation for pre-harvest handling in post-harvest broccoli storage.

Selection, Identification, and Transcript Expression Analysis of Antioxidant Enzyme Genes in Neoseiulus barkeri after Short-Term Heat Stress.

Phytoseiid mite Neoseiulus barkeri is a crucial biological control agent utilized to control pest mites and many insects in crops all over the world. However, they are vulnerable to multiple environmental pressures, with high-temperature stress being the most significant challenge. Heat stress disrupts the balance of reactive oxygen species (ROS) levels in organisms, resulting in oxidative stress within the body. Antioxidant enzymes play a crucial role in effectively neutralizing and clearing ROS. In this study, comparative transcriptomics and quantitative real-time PCR (qRT-PCR) were employed to assess the impact of short-term heat stress on the transcript expression of antioxidant enzyme genes in N. barkeri. We primarily identified four antioxidant enzyme genes (NbSOD, NbPrx, NbCAT, and NbGPX) in N. barkeri after exposure to short-term heat stress. Then, new data on the expression patterns of these genes were generated. RNA sequencing and bioinformatics analysis revealed that NbSOD belongs to the Fe/Mn family of superoxide dismutase (SOD), which was identified as MnSOD. NbPrx was classified as a 1-Cys peroxiredoxin of the peroxidase family, whereas NbCAT was recognized as a classical catalase, and NbGPX was determined as cytoplasmic glutathione peroxidase-1 (GPX1). Transcriptional expression analysis of these four genes was conducted at different high temperatures: 36 °C, 38 °C, and 40 °C for 2, 4, and 6 h. The results also showed that all four genes exhibited significant up-regulation in response to short-term heat stress. Similarly, the highest expression levels for NbSOD, NbPrx, and NbCAT were observed at 40 °C for 4 h. However, NbGPX displayed its maximum expression value at 38 °C for 4 h. Overall, the obtained data suggest that short-term heat stress increases levels of ROS generated inside living organisms, which disrupts the oxidative balance and leads to alterations in the expression levels of antioxidant enzyme genes.

Construction of multifunctional coating with cationic amino acid-coupled peptides for osseointegration of implants

Osseointegration is an important indicator of implant success. This process can be improved by coating modified bioactive molecules with multiple functions on the surface of implants. Herein, a simple multifunctional coating that could effectively improve osseointegration was prepared through layer-by-layer self-assembly of cationic amino acids and tannic acid (TA), a negatively charged molecule. Osteogenic growth peptide (OGP) and the arginine-glycine-aspartic acid (RGD) functional polypeptides were coupled with Lys6 (K6), the two polypeptides then self-assembled with TA layer by layer to form a composite film, (TA-OGP@RGD)n. The surface morphology and biomechanical properties of the coating were analyzed in gas and liquid phases, and the deposition process and kinetics of the two peptides onto TA were monitored using a quartz crystal microbalance. In addition, the feeding consistency and adsorption ratios of the two peptides were explored by using fluorescence visualization and quantification. The (TA-OGP@RGD)n composite membrane mediated the early migration and adhesion of cells and significantly promoted osteogenic differentiation and mineralization of the extracellular matrix in vitro. Additionally, the bifunctional peptide exhibited excellent osteogenesis and osseointegration owing to the synergistic effect of the OGP and RGD peptides in vivo. Simultaneously, the (TA-OGP@RGD)n membrane regulated the balance of reactive oxygen species in the cell growth environment, thereby influencing the complex biological process of osseointegration. Thus, the results of this study provide a novel perspective for constructing multifunctional coatings for implants and has considerable application potential in orthopedics and dentistry.

Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.

A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death. ROS are signal transducers that induce angiogenesis, invasion, cell migration, and proliferation at low to moderate concentrations and are considered normal by-products of a range of biological activities. Although ROS is known to exist in the oncology domain since time immemorial, its excessive quantities are known to damage organelles, membranes, lipids, proteins, and nucleic acids, resulting in cell death. In the last two decades, numerous studies have demonstrated immunotherapies and other anticancer treatments that modulate ROS levels have promising in vitro and in vivo effects. This review also explores recent targets for therapeutic interventions in cancer that are based on ROS generation or inhibition to disrupt the cell oxidative stress balance. Examples include-metabolic targets, targeted therapy with biomarkers, natural extracts and nutraceuticals and targets developed in the area of nano medicine. In this review, we present the molecular pathways which can be used to create therapy plans that target cancer by regulating ROS levels, particularly current developments and potential prospects for the effective implementation of ROS-mediated therapies in clinical settings. The recent advances in complex interaction with apoptosis especially ferroptosis and its role in epigenomics and modifications are a new paradigm, to just mechanical action of ROS, as highlighted in this review. Their inhibition by nutraceuticals and natural extracts has been a scientific challenging avenue that is explored. Also, the inhibition of generation of ROS by inhibitors, immune modulators and inhibitors of apoptosis and ferroptosis is explored in this review.

Iron-Dependent Cell Death: A New Treatment Approach against Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating tumor type where a very high proportion of people diagnosed end up dying from cancer. Surgical resection is an option for only about 20% of patients, where the 5-year survival increase ranges from 10 to 25%. In addition to surgical resection, there are adjuvant chemotherapy schemes, such as FOLFIRINOX (a mix of Irinotecan, oxaliplatin, 5-Fluorouraci and leucovorin) or gemcitabine-based treatment. These last two drugs have been compared in the NAPOLI-3 clinical trial, and the NALIRIFOX arm was found to have a higher overall survival (OS) (11.1 months vs. 9.2 months). Despite these exciting improvements, PDAC still has no effective treatment. An interesting approach would be to drive ferroptosis in PDAC cells. A non-apoptotic reactive oxygen species (ROS)-dependent cell death, ferroptosis was first described by Dixon et al. in 2012. ROS are constantly produced in the tumor cell due to high cell metabolism, which is even higher when exposed to chemotherapy. Tumor cells have detoxifying mechanisms, such as Mn-SOD or the GSH-GPX system. However, when a threshold of ROS is exceeded in the tumor cell, the cell's antioxidant systems are overwhelmed, resulting in lipid peroxidation and, ultimately, ferroptosis. In this review, we point out ferroptosis as an approach to consider in PDAC and propose that altering the cellular ROS balance by combining oxidizing agents or with inhibitors of the main cellular detoxifiers triggers ferroptosis in PDAC.