Reactive Oxygen Species Activity Research Articles

Novel in silico screening system for plant defense activators using deep learning-based prediction of reactive oxygen species accumulation

BackgroundPlant defense activators offer advantages over pesticides by avoiding the emergence of drug-resistant pathogens. However, only a limited number of compounds have been reported. Reactive oxygen species (ROS) act as not only antimicrobial agents but also signaling molecules that trigger immune responses. They also affect various cellular processes, highlighting the potential ROS modulators as plant defense activators. Establishing a high-throughput screening system for ROS modulators holds great promise for identifying lead chemical compounds with novel modes of action (MoAs).ResultsWe established a novel in silico screening system for plant defense activators using deep learning-based predictions of ROS accumulation combined with the chemical properties of the compounds as explanatory variables. Our screening strategy comprised four phases: (1) development of a ROS inference system based on a deep neural network that combines ROS production data in plant cells and multidimensional chemical features of chemical compounds; (2) in silico extensive-scale screening of seven million commercially available compounds using the ROS inference model; (3) secondary screening by visualization of the chemical space of compounds using the generative topographic mapping; and (4) confirmation and validation of the identified compounds as potential ROS modulators within plant cells. We further characterized the effects of selected chemical compounds on plant cells using molecular biology methods, including pathogenic signal-triggered enzymatic ROS induction and programmed cell death as immune responses. Our results indicate that deep learning-based screening systems can rapidly and effectively identify potential immune signal-inducible ROS modulators with distinct chemical characteristics compared with the actual ROS measurement system in plant cells.ConclusionsWe developed a model system capable of inferring a diverse range of ROS activity control agents that activate immune responses through the assimilation of chemical features of candidate pesticide compounds. By employing this system in the prescreening phase of actual ROS measurement in plant cells, we anticipate enhanced efficiency and reduced pesticide discovery costs. The in-silico screening methods for identifying plant ROS modulators hold the potential to facilitate the development of diverse plant defense activators with novel MoAs.

Pitavastatin induces caspase-mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line.

Pitavastatin (PITA) is a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti-cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5-200 μM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h. Cell apoptosis and cell cycle analyses were performed in flow cytometry (0.1-100 μM). The evaluation of genotoxic effects and oxidative DNA damage of PITA (2-200 μM) were performed with standard comet assay, formamidopyrimidine glycosylase (fpg)-modified comet assay, and reactive oxygen species (ROS) activation in HeLa cells. PITA alone reduced cell viability in a dose-dependent manner (20-200, 20-200, and 5-200 μM for 24, 48, and 72 h, respectively, in MTT). The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly at 100 μM for 4 h and 20 μM for 24 h, respectively. PITA-induced apoptosis, an increased proportion of sub G1 cells, was monitored, and also, it increased the expression of active caspase-9 and caspase-3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) by western blotting and caspase 3/8/9 multiple assay kit. We conclude that PITA can be used to efficiently cervical cancer studies, and promising findings have been obtained for further studies.

Understanding how MSCs reverse radiation-induced fibrosis: HGF vs. TGF-B1

Understanding how MSCs reverse radiation-induced fibrosis: HGF <i>vs.</i> TGF-B1

The enzymatic hydrolysates of Andrias davidianus mucus alleviates UVA-induced photoaging in the HSF cell and mouse skin

Photoaging is the premature aging of skin caused by long-term exposure to ultraviolet radiation. The skin mucus of Andrias davidianus has anti-photoaging activity, but its active ingredients and mechanisms are not clear. In this study, we first investigated the photoprotective effect of enzymatic hydrolysates from Andrias davidianus mucus (AD-APRO) on UVA-irradiated responses in human skin fibroblasts (HSF) cells and mice. AD-APRO hindered the UVA induced activation of reactive oxygen species (ROS) and increased the activity of antioxidase in HSF cells. Furthermore, topical application of AD-APRO ameliorated skin photoaging in a mouse model by suppressing oxidative stress. CAMP and Peptide Ranker, two online tools, were used to predict the active peptides of AD-APRO against photoaging. The active peptides of AD-APRO were predicted to be KDACCNLVLHFNPRF, NLVLHFNPRF, FEWKP, and CNLVLHFNPRF. These results provide a basis for the study of the photoprotective effect of AD-APRO and suggest that it can be potentially used as an agent against UVA-induced skin photoaging in humans.&#x0D;

Shoot Maturation Strengthens FLS2-Mediated Resistance to Pseudomonas syringae.

Temporospatial regulation of immunity components is essential for properly activating plant defense response. Flagellin-sensing 2 (FLS2) is a surface-localized receptor that recognizes bacterial flagellin. The immune function of FLS2 is compromised in early stages of shoot development. However, the underlying mechanism for the age-dependent FLS2 signaling is not clear. Here, we show that the reduced basal immunity of juvenile leaves against Pseudomonas syringae pv. tomato DC3000 is independent of FLS2. The flg22-induced marker gene expression and reactive oxygen species activation were comparable in juvenile and adult stages, but callose deposition was more evident in the adult stage than the juvenile stage. We further demonstrated that microRNA156, a master regulator of plant aging, does not influence the expression of FLS2 and FRK1 (Flg22-induced receptor-like kinase 1) but mildly suppresses callose deposition in juvenile leaves. Our experiments revealed an intrinsic mechanism that regulates the amplitude of FLS2-mediated resistance during aging. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The Role of Reactive Oxygen Species in the Regulation of Blood Vessel Tone in Perinatal and Early Postnatal Ontogenesis

Reactive oxygen species (ROS) have been considered for many years as negative regulators in the cardiovascular system. Indeed, excessive production of ROS characterizes many cardiovascular diseases. The damaging effect of ROS can be especially pronounced in a newborn organism, since during this period their contractile effect in pulmonary arteries remains as high as in the pre-term fetus arteries and the antioxidant systems have not yet formed. Therefore, in the first hours and days of independent life, pulmonary arteries tend to contract, primarily due to the low bioavailability of endothelial NO, which increases the risk of developing pulmonary hypertension in newborns. At the same time, during the perinatal period, ROS play an important role in the adaptive reactions of the circulatory system. ROS provide occlusion of the ductus arteriosus and separation of the pulmonary and systemic circulations soon after birth, and also contribute to the contraction of peripheral vessels during hypoxia, which often accompanies the delivery, and therefore provide priority blood supply to the brain in these conditions. The vasomotor effect of ROS is also pronounced in early postnatal ontogenesis, but it has a different character. In the first weeks of life, the action of ROS serves as one of the mechanisms for increasing endothelium-dependent relaxation of pulmonary vessels. In addition, during early postnatal ontogeny, ROS may play an important role in the regulation of systemic vascular tone. This review outlines the current understanding of the vasomotor role of ROS in the vessels of the pulmonary and systemic circulation and considers the mechanisms of ROS effects on the functioning of vascular endothelial and smooth muscle cells in the perinatal and early postnatal periods.

Photodynamic-responsive gelatin-based coating with high utilization curcumin loaded bilayer nanoencapsulation: A promising environmental food packaging

The development and application of curcumin-mediated antimicrobial photodynamic techniques (PDT) in food preservation are highly anticipated to resist microbial contamination and prevent food spoilage. In this study, high-utilization curcumin-loaded bilayer nanoencapsulation was prepared to incorporated into a gelatin-based edible coating for beef preservation. Bilayer nanoencapsulation composed of shellac and poly-γ-glutamic acid (CS-NPs) improved the encapsulation efficiency of shellac to curcumin by >1.5 times. The incorporation of CS-NPs improved the compact of coating structure with hydrogen bonds. In food simulants, coatings possessed control release properties and the release mechanism was Fick diffusion (without the addition of γ-PGA) and non-Fick diffusion (with the addition of γ-PGA). These prepared coatings exhibited excellent barrier, antibacterial (antibacterial ratio > 95 %), and antioxidant properties (scavenging ratio > 90 %). Curcumin mediated antimicrobial photodynamic techniques (PDT) of the coatings were verified with the activity of blue light-induced reactive oxygen species (ROS). The shelf-life of beef was extended by the coating with blue light. In summary, the design of bilayer CS-NPs significantly improved the utilization of curcumin which provided a high-efficiency strategy for PDT-responsive food packaging with environmental practical.

Mild traumatic brain injury in Drosophila melanogaster alters reactive oxygen and nitrogen species in a sex-dependent manner

Traumatic brain injury (TBI) is an outside force causing a modification in brain function and/or structural brain pathology that upregulates brain inducible nitric oxide synthase (iNOS), instigating increased levels of nitric oxide activity which is implicated in secondary pathology leading to behavioral deficits (Hall et al., 2012; Garry et al., 2015; Kozlov et al., 2017). In mammals, TBI-induced NO production activates an immune response and potentiates metabolic crisis through mitochondrial dysfunction coupled with vascular dysregulation; however, the direct influence on pathology is complicated by the activation of numerous secondary cascades and activation of other reactive oxygen species. Drosophila TBI models have demonstrated key features of mammalian TBI, including temporary incapacitation, disorientation, motor deficits, activation of innate immunity (inflammation), and autophagy responses observed immediately after injury (Katzenberger et al., 2013; Barekat et al., 2016; Simon et al., 2017; Anderson et al., 2018; Buhlman et al., 2021b). We hypothesized that acute behavioral phenotypes would be associated with deficits in climbing behavior and increased oxidative stress. Because flies lack mammalian-like cardiovascular and adaptive immune systems, we were able to make our observations in the absence of vascular disruption and adaptive immune system interference in a system where highly targeted interventions can be rapidly evaluated.To demonstrate the induction of injury, ten-day-old transgenic flies received an injury of increasing angles from a modified high impact trauma (HIT) device where angle-dependent increases occurred for acute neurological behavior assessments and twenty-four-hour mortality, and survival was significantly decreased. Injury caused sex-dependent effects on climbing activity and measures of oxidative stress. Specifically, after a single 60-degree HIT, female flies exhibited significant impairments in climbing activity beyond that observed in male flies. We also found that several measures of oxidative stress, including Drosophila NOS (dNOS) expression, protein nitration, and hydrogen peroxide production were significantly decreased in female flies. Interestingly, protein nitration was also decreased in males, but surpassed sham levels with a more severe injury. We also observed decreased autophagy demand in vulnerable dopaminergic neurons in female, but not male flies. In addition, mitophagy initiation was decreased in females.Collectively, our data suggest that TBI in flies induces acute behavioral phenotypes and climbing deficits that are analogous to mammalian TBI. We also observed that various indices of oxidative stress, including dNOS expression, protein tyrosine nitration, and hydrogen peroxide levels, as well as basal levels of autophagy, are altered in response to injury, an effect that is more pronounced in female flies.

Self-Assembled Nano-CT Contrast Agent Leveraging Size Aggregation for Improved In Vivo Tumor CT Imaging.

Computed tomography (CT) is a widely utilized noninvasive diagnostic tool in clinical practice. However, the commonly employed small molecular iodinated contrast agents (ICAs) in clinical CT imaging have limitations such as nonspecific distribution in body, rapid clearance through kidneys, etc., leading to a narrow imaging time window. In contrast, existing nano-sized ICAs face challenges like structural uncertainty, poor reproducibility, low iodine content, and uniformity issues. In this study, a novel approach is presented utilizing the aggregation-induced emission luminogen (AIEgen) to design and fabricate a kind of monocomponent nano-sized ICA (namely, BioDHU-CT NPs) that exhibits a unique aggregation effect upon activation. The small sized BioDHU-CT nanoparticles exhibit excellent tumor targeting capabilities and can release ICA modified with AIEgen with a high release efficiency up to 88.45%, under the activation of reactive oxygen species highly expressed in tumor regions. The released ICA performs in situ aggregation capability in the tumor region, which can enhance the retention efficiency of CT contrast agents, extending the imaging time window and improving the imaging quality in tumor regions.

Effect of melatonin foliar sprays on morphophysiological attributes, fruit yield and quality of Momordica charantia L. under salinity stress

Soil salinity is one of the increasing problems in agricultural fields in many parts of the world, adversely affecting the performance and health of the plants. As a pleiotropic signal and antioxidant molecule in both animals and plants, melatonin has been reported to possess significant roles in combating with stress factors, in general and salt stress, in particular. In this study, the interactive effects of melatonin (0, 75, and 150 μM) and salt stress (0, 50 and 100 mM NaCl) were investigated by assaying the some agronomic, physlogical and biochemical attributes and essential oil compounds of bitter melon (Momordica charantia). The results showed that exogenous melatonin could promote net photosynthetic rate (Pn) and PSII efficiency (Fv/Fm), increase K+ content and activity of antioxidant enzymes and decrease reactive oxygen species, malondialdehyde and Na+ content in stress-submitted seedlings, in comparison to the non-stressed seedlings (p < 0.05). Melatonin increased content of essential oils. Concerning the major compounds of fruits of bitter melon, charantin, momordicin and cucurbitacin were increased with the melatonin treatments, whereas they were critically decreased with the salt stress. In addition, melatonin increased the antioxidant capacity in fruits under non-saline and salinity conditions. Amid the concentrations of melatonin, plants treated with 150 μM of melatonin under either non-saline or saline conditions showed better performance and productivity. Therefore, application of 150 μM melatonin resulted in a significant improvement of salinity tolerance and essential oil compounds in bitter melon plant, suggesting this as an efficient ‘green’ strategy for sustainable crop production under salt stress conditions.

Characterization of a Bacillus velezensis strain as a potential biocontrol agent against soft rot of eggplant fruits

Postharvest soft rot of eggplant fruits caused by Pectobacterium carotovorum is a bacterial disease with a high disease incidence and produces substantial economic losses. This study aimed to control postharvest soft rot of eggplant fruits by Bacillus velezensis and investigate the possible control mechanisms based on the effects of B. velezensis on P. carotovorum subsp. carotovorum (Pcc) and eggplant fruits, respectively. B. velezensis effectively controlled postharvest soft rot of eggplant fruits and directly inhibited Pcc growth in vitro. The volatile metabolites produced by B. velezensis showed no inhibition on Pcc. Whereas the cell-free filtrate of B. velezensis significantly inhibited the growth of Pcc in vitro and in vivo. Notably, methanol-soluble precipitates obtained from cell-free filtrate showed significant inhibition on Pcc, and the primary inhibitory substances were identified as surfactin isoforms. Besides, iturin and fengycin isoforms with much lower relative abundance were also detected in the methanol-soluble precipitates. Furthermore, B. velezensis enhanced the activities of reactive oxygen species (ROS) scavenging enzymes in eggplant fruits that alleviated ROS and oxidative damage; thereby, B. velezensis enhanced the fruits' disease resistance.

Synergistic and Additive Effects of Menadione in Combination with Antibiotics on Multidrug-Resistant Staphylococcus aureus: Insights from Structure-Function Analysis of Naphthoquinones.

Antimicrobial resistance (AMR) interferes with the effective treatment of infections and increases the risk of microbial spread and infection-related illness and death. The synergistic activities of combinations of antimicrobial compounds offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 group at C2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphylococcus aureus and its biofilms. We found an additive (0.5<FICI 1.0) and synergistic (FICI≤0.5) effect of menadione with ciprofloxacin and ampicillin, respectively. High reactive oxygen species (ROS) activity and inhibition of biofilm formation (>90 %) were also observed. However, preformed biofilms were not affected. Dent formation was also evident in S. aureus treated with the test compounds. The structure-function relationship (SFR) of NQs was used to determine and predict their activity pattern against pathogens. Analysis of 10 structurally distinct NQs revealed that the compounds with -Cl, -Br, -CH3 , or -OH groups displayed the lowest MICs (32-256 μg/mL). Furthermore, 1,4-NQs possessing a halogen or -CH3 moiety showed elevated ROS activity, whereas molecules with an -OH group affected cell integrity. Improved activity of antimicrobial combinations and SFR approaches are significant in antimicrobial therapies.

Ginsenoside compound-K attenuates OVX-induced osteoporosis via the suppression of RANKL-induced osteoclastogenesis and oxidative stress

Osteoporosis (OP), a systemic and chronic bone disease, is distinguished by low bone mass and destruction of bone microarchitecture. Ginsenoside Compound-K (CK), one of the metabolites of ginsenoside Rb1, has anti-aging, anti-inflammatory, anti-cancer, and hypolipidemic activities. We have demonstrated CK could promote osteogenesis and fracture healing in our previous study. However, the contribution of CK to osteoporosis has not been examined. In the present study, we investigated the effect of CK on osteoclastogenesis and ovariectomy (OVX)-induced osteoporosis. The results showed that CK inhibited receptor activator for nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation and reactive oxygen species (ROS) activity by inhibiting the phosphorylation of NF-κB p65 and oxidative stress in RAW264.7 cells. In addition, we also demonstrated that CK could inhibit bone resorption using bone marrow-derived macrophages. Furthermore, we demonstrated that CK attenuated bone loss by suppressing the activity of osteoclast and alleviating oxidative stress in vivo. Taken together, these results showed CK could inhibit osteoclastogenesis and prevent OVX-induced bone loss by inhibiting NF-κB signaling pathway.Graphical

High glucose enhances the activation of NLRP3 inflammasome by ambient fine particulate matter in alveolar macrophages

BackgroundEpidemiological studies have demonstrated that individuals with preexisting conditions, including diabetes mellitus (DM), are more susceptible to air pollution. However, the underlying mechanisms remain unclear. In this study, we proposed that a high glucose setting enhances ambient fine particulate matter (PM2.5)-induced macrophage activation and secretion of the proinflammatory cytokine, IL-1β, through activation of the NLRP3 inflammasome, altering the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).ResultsExposure of mouse alveolar macrophages to non-cytotoxic doses of PM2.5 led to upregulation of IL-1β, activation of the NLRP3 inflammasome, increased nuclear translocation of the transcription factor NF-κB, increased generation of reactive oxygen species (ROS), and increased expression and enzymatic activity of MMP-9; these effects were enhanced when cells were pretreated with high glucose. However, pretreatment in a high glucose setting alone did not induce significant changes. ROS generation following PM2.5 exposure was abolished when cells were pretreated with ROS scavengers such as Trolox and superoxide dismutase (SOD), or with an NADPH oxidase inhibitor, DPI. Pretreatment of cells with DPI attenuated the effects of a high glucose setting on PM2.5-induced upregulation of IL-1β, activation of the NLRP3 inflammasome, and nuclear translocation of NF-κB. In addition, enhancement of PM2.5-induced expression and enzymatic activity of MMP-9 following high glucose pretreatment was not observed in primary alveolar macrophages obtained from NLRP3 or IL-1R1 knockout (KO) mice, where pro-IL-1β cannot be cleaved to IL-1β or cells are insensitive to IL-1β, respectively.ConclusionsThis study demonstrated that exposure of mouse alveolar macrophages to PM2.5 in a high glucose setting enhanced PM2.5-induced production of IL-1β through activation of the NLRP3 inflammasome and nuclear translocation of NF-κB due to PM2.5-induced oxidative stress, leading to MMP-9 upregulation. The key role of NADPH oxidase in PM2.5-induced ROS generation and activation of the IL-1β secretion pathway and the importance of IL-1β secretion and signaling in PM2.5-induced increases in MMP-9 enzymatic activity were also demonstrated. This study provides a further understanding of the potential mechanisms underlying the susceptibility of individuals with DM to air pollution and suggests potential therapeutic targets.

Overexpression of a C3HC4‐type E3‐ubiquitin ligase contributes to salinity tolerance by modulating Na+ homeostasis in rice

AbstractSoil salinity has a negative effect on crop yield. Therefore, plants have evolved many strategies to overcome decreases in yield under saline conditions. Among these, E3‐ubiquitin ligase regulates salt tolerance. We characterized Oryza sativa Really Interesting New Gene (RING) Finger C3HC4‐type E3 ligase (OsRFPHC‐4), which plays a positive role in improving salt tolerance. The expression of OsRFPHC‐4 was downregulated by high NaCl concentrations and induced by abscisic acid (ABA) treatment. GFP‐fused OsRFPHC‐4 was localized to the plasma membrane of rice protoplasts. OsRFPHC‐4 encodes a cellular protein with a C3HC4‐RING domain with E3 ligase activity. However, its variant OsRFPHC‐4C161A does not possess this activity. OsRFPHC‐4‐overexpressing plants showed enhanced salt tolerance due to low accumulation of Na+ in both roots and leaves, low Na+ transport in the xylem sap, high accumulation of proline and soluble sugars, high activity of reactive oxygen species (ROS) scavenging enzymes, and differential regulation of Na+/K+ transporter expression compared to wild‐type (WT) and osrfphc‐4 plants. In addition, OsRFPHC‐4‐overexpressing plants showed higher ABA sensitivity under exogenous ABA treatment than WT and osrfphc‐4 plants. Overall, these results suggest that OsRFPHC‐4 contributes to the improvement of salt tolerance and Na+/K+ homeostasis via the regulation of changes in Na+/K+ transporters.

Melatonin induces RAW264.7 cell apoptosis via the BMAL1/ROS/MAPK-p38 pathway to improve postmenopausal osteoporosis.

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene. Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway. Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis.

Effect and mechanism of Banxia Xiexin decoction in colorectal cancer: A network pharmacology approach

BackgroundBanxia Xiexin decoction (BXD) is a traditional Chinese medicine with anti-colorectal cancer (CRC) activity. However, its bioactive constituents and its mechanism of action remain unclear. Herein, we explored the mechanism of action of BXD against CRC using a network pharmacology approach. MethodsFirst, the targets of the main chemical components of BXD were predicted and collected through a database, and the intersection of compound targets and disease targets was obtained. Subsequently, protein–protein interaction network analysis, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the potential mechanisms underlying the effects of BXD on CRC. Finally, a CRC cell model and a CRC xenograft model in nude mice were utilized to further determine the mechanism of action. ResultsA compound–therapeutic target network of BXD was constructed, revealing 146 cellular targets of BXD. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling axis was identified as the main target of BXD. Using in vitro and in vivo models, the activity of BXD against CRC was found to be mediated through ferritinophagy by targeting the PI3K/AKT/mTOR axis, leading to intracellular iron accumulation, reactive oxygen species activation, and finally ferroptosis. ConclusionsThrough the application of network pharmacology and in vitro/in vivo validation experiments, we discovered that BXD exerts anti-CRC effects via the ferritinophagy pathway. Furthermore, we elucidated the potential mechanism underlying its induction of ferritinophagy. These findings demonstrate the significant potential of traditional drugs in managing CRC and support their wider clinical application in combination chemotherapy, targeted therapy, and immunotherapy.

Ti3+/Ti4+ and Co2+/Co3+ redox couples in Ce-doped Co-Ce/TiO2 for enhancing photothermocatalytic toluene oxidation

Cerium and cobalt loaded Co-Ce/TiO2 catalyst prepared by impregnation method was investigated for photothermal catalytic toluene oxidation. Based on catalyst characterizations (XPS, EPR and H2-TPR), redox cycle between Co and TiO2 (Co2+ + Ti4+ ↔ Co3+ + Ti3+) results in the formation of Co3+, Ti3+ and oxygen vacancies, which play important roles in toluene catalytic oxidation reaction. The introduction of Ce brings in the dual redox cycles (Co2+ + Ti4+ ↔ Co3+ + Ti3+, Co2+ + Ce4+ ↔ Co3+ + Ce3+), further promoting the elevation of reaction sites amount. Under full spectrum irradiation with light intensity of 580 mW/cm2, Co-Ce/TiO2 catalyst achieved 96% of toluene conversion and 73% of CO2 yield, obviously higher than Co/P25 and Co/TiO2. Co-Ce/TiO2 efficiently maintains 10-hour stability test under water vapor conditions and exhibits better photothermal catalytic performance than counterparts under different wavelengths illumination. Photothermal catalytic reaction displays improved activities compared with thermal catalysis, which is attributed to the promotional effect of light including photocatalysis and light activation of reactive oxygen species.

A Novel Endoplasmic Reticulum-Targeted Metal-Organic Framework-Confined Ruthenium (Ru) Nanozyme Regulation of Oxidative Stress for Central Post-Stroke Pain.

Central post-stroke pain (CPSP) is a chronic neuropathic pain caused by cerebrovascular lesion or disfunction after stroke. Convincing evidence suggest that excessive reactive oxygen species (ROS), generated matrix metalloproteinase (MMPs) and neuroinflammation are largely involved in the development of pain. In this study, an effective strategy is reported for treating pain hypersensitivity using an endoplasmic reticulum (ER)-targeted metal-organic framework (MOF)-confined ruthenium (Ru) nanozyme. The Ru MOF is coated with a p-dodecylbenzene sulfonamide (p-DBSN) modified liposome with endoplasmic reticulum-targeted function. The experimental results reveals that ROS, Emmprin, MMP-2, and MMP-9 are upregulated in the brain of CPSP mice, along with the elevated expression of inflammation markers such as TNF-α and IL-6. Compared to vehicle, one-time intravenous administration of ER-Ru MOF significantly reduces mechanical hypersensitivity after CPSP for three days. Overall, ER-Ru MOF system can inhibit oxidative stress in the brain tissues of CPSP model, reduce MMPs expression, and suppress neuroinflammation response-induced injury, resulting in satisfactory prevention and effective treatment of CPSP during a hemorrhagic stroke. The ER-Ru MOF is expected to be useful for the treatment of neurological diseases associated with the vicious activation of ROS, based on the generality of the approach used in this study.

2,5-Dihydroxyacetophenone attenuates RANKL-mediated osteoclastogenesis by affecting the NFATc1 signaling pathway in vitro

Excessive bone resorption activity of osteoclasts is a common characteristic of osteolytic conditions such as osteoporosis and inflammatory bone diseases. Natural compounds with antiosteoclastogenic function seem to be beneficial for the treatment of osteolytic diseases. In this study, we evaluated the effects of 2,5-dihydroxyacetophenone (DHAP), a phenolic compound in Ganoderma bambusicola, on osteoclastogenesis induced in vitro by the receptor activator of nuclear factor-κB ligand (RANKL). DHAP inhibited the differentiation, actin ring formation, and bone resorption activity of osteoclasts. In particular, DHAP inhibited the transcriptional activity of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) during osteoclastogenesis. This inhibition resulted in reduced expression levels of cathepsin k (Ctsk), tartrate-resistant acid phosphatase (Trap), and NFATc1 (Nfatc1), thereby reducing the differentiation of osteoclasts. However, DHAP did not affect reactive oxygen species production or activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) signaling. Our findings suggest that DHAP inhibits RANKL-induced osteoclastogenesis by inhibiting the NFATc1 signaling pathway.