Search Results (939)

Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H₂O₂-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H₂O₂-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article

Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU treatment. Nonetheless, the efficacy of existing SIRT3 agonists remains suboptimal. Methods: Here, we introduce a novel compound, SZC-6, demonstrating promising activity levels. Results: SZC-6 treatment down-regulated the expression of inflammatory factors in LPS-treated RAW264.7 cells and reduced the proportion of M1 macrophages. Mitosox, IF, and JC-1 staining revealed that SZC-6 preserved cellular mitochondrial homeostasis and reduced the accumulation of reactive oxygen species. In vivo experiments demonstrated that SZC-6 treatment accelerated wound healing in diabetic mice. Furthermore, HE and Masson staining revealed increased neovascularization at the wound site with SZC-6 treatment. Tissue immunofluorescence results indicated that SZC-6 effectively decreased the proportion of M1-like cells and increased the proportion of M2-like cells at the wound site. We also found that SZC-6 significantly reduced MyD88, p-IκBα, and NF-χB p65 protein levels and inhibited the nuclear translocation of P65 in LPS-treated cells. Conclusions: The study concluded that SZC-6 inhibited the activation of the NF-χB pathway, thereby reducing the inflammatory response and promoting skin healing in diabetic ulcers. SZC-6 shows promise as a small-molecule compound for promoting diabetic wound healing. Full article

Parishin C (PaC) is an active ingredient in Gastrodia elata Bl. that has neuroprotective effects. However, research on its role in oxidative stress and neuroinflammation is still limited. This study used LPS–stimulated HT22 cells to investigate the antioxidant properties of PaC. Through the co–culture system of HT22 and BV2 cells, the effect of PaC on neuroinflammation was explored. The current results indicated that PaC can inhibit the levels of reactive oxygen species and peroxides in LPS–stimulated HT22 cells and increase the levels of antioxidant factors. Meanwhile, PaC can also inhibit neuronal ferroptosis and the levels of pro–inflammatory cytokines in BV2 cells. Importantly, the antioxidant and anti–inflammatory effects of PaC are achieved by activating the Nrf2 signaling pathway. The WB and IF results indicated that PaC can promote nuclear translocation of Nrf2, activate downstream antioxidant factors, and thereby regulate inflammatory responses. Inhibition of Nrf2 can significantly inhibit the regulation of PaC on the Nrf2 signaling pathway. These results indicated that PaC can activate the Nrf2 signaling pathway to inhibit oxidative stress and inflammation. Full article

Lymphoma is the most common neoplasm of lymphoid tissues in dogs. Exportin 1 (XPO1) is an important major nuclear receptor for exporting proteins and RNA species. The XPO1 upregulation can eliminate some tumor suppressor proteins (TSPs) function upon their nuclear–cytoplasmic export. The XPO1 inhibitor, KPT-335, blocks the translocation of TSPs and restores their function to induce cell cycle arrest, apoptosis, and cell proliferation. This in vitro study aimed to evaluate the XPO1 mRNA and protein expression in canine lymphoma cell lines and confirm the relevance with KPT-335. XPO1 mRNA and protein levels were quantified, and the effect of KPT-335 was assessed by a cell proliferation assay. The results indicated that XPO1 mRNA and protein were highly expressed in 17-71, CLBL-1, CLC, CLGL-90, and UL-1, and were moderately expressed in GL-1, Ema, and Nody-1. All canine lymphoma cell lines showed dose-dependent growth inhibition and decreased cell viability in response to KPT-335, with IC₅₀ concentrations ranged from 89.8–418 nM. The expression levels of XPO1 mRNA and protein were related; however, no correlation was found between those expression levels and the efficacy of KPT-335. These findings suggest that XPO1 may represent a promising target for therapeutic intervention in canine lymphoma. Full article

Glyphosate has been used for roadside weed control in southern Spain for over 40 years, and most populations of goldentop (Lamarckia aurea L.) Moench have putatively developed resistance to this active ingredient. The physiological and biochemical basis for glyphosate resistance in this weed has been investigated. Dose–response studies indicated that the resistant biotype (R) was almost 13 times more resistant to glyphosate compared to a known susceptible biotype (S). Studies of foliar glyphosate retention and ¹⁴C-glyphosate uptake/translocation showed no significant differences between both L. aurea biotypes. Basal 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity (µmol µg⁻¹TSP min⁻¹) showed similar values between R (0.82 ± 0.04) and S (0.75 ± 0.05) biotypes. On the other hand, the resistance factor (I₅₀R/I₅₀S) did not show a difference between the two biotypes. Therefore, it was concluded that target-site (TSR) resistance mechanisms are not involved in glyphosate resistance in this weed species. The metabolism of glyphosate to form the non-toxic metabolites aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine was greater and faster in the R compared to the S biotype; thus, glyphosate resistance is due to non-target-site resistance (NTSR) mechanisms. This paper is the first report of glyphosate resistance in L. aurea in the world. Full article

This study investigates growth responses, heavy metal (Cd, As) uptake, translocation, and mineral nutrient regulation in leafy vegetables with varying heavy metal tolerance, addressing the threat posed by combined Cd and As pollution. Three high-tolerance, four moderate-tolerance, and one sensitive leafy vegetable were grown in Cd+As-contaminated hydroponics. Post-harvest yields and concentrations of Cd, As, and trace elements were assessed. Results showed that (1) compared with single heavy metal treatments, the combination of Cd and As significantly increased the translocation factor of Cd in black bean sprouts and white radish sprouts by up to 83.83% and 503.2%; (2) changes in mineral nutrient concentrations in leafy vegetables were similar between single and combined heavy metal stresses, but the regulatory patterns varied among different leafy vegetable species; (3) under Cd/As exposure, high-tolerance leafy vegetables (e.g., pak choi) had strong heavy metal accumulation abilities, and heavy metal stress positively regulated mineral elements in their roots; In contrast, sensitive leafy vegetables (e.g., pea sprouts) often exhibited suppressed mineral element content in their roots, which was a result of their strategy to reduce heavy metal uptake. These results offer key insights into resistance mechanisms against combined heavy metal pollution in leafy vegetables, supporting phytoremediation efforts and safe production. Full article

Soil contamination with toxic inorganic elements poses a major challenge to rice cultivation, affecting plant physiology, yield, and grain safety. While natural variation in tolerance exists among rice genotypes and related species, recent advances in genomics, breeding, and biotechnology offer new opportunities to enhance adaptation. This review synthesizes the current knowledge on the physiological effects of toxic elements and explores strategies to improve tolerance, from harnessing genetic diversity to genome editing and transgenic approaches. Attention is also paid to the role of microbiota in mitigating toxicity and reducing translocation to seeds, highlighting emerging solutions for sustainable rice production in contaminated environments. Full article

A sudden increase in ambient oxygen concentration after birth forces the metabolic switch from anaerobic glycolysis to oxidative phosphorylation, which contributes to the rapid decline of cardiomyocyte proliferation. Lactate dehydrogenase A (LDHA), a metabolic enzyme normally localized in the cytoplasm, has been reported to regulate cardiomyocyte proliferation via inducing metabolic reprogramming. Nuclear LDHA has been observed in multiple proliferative cells, whereas the role of LDHA nuclear translocation in cardiomyocyte proliferation remains unresolved. Here we found that the expression of nuclear LDHA was induced both in the infarct area of myocardial infarction (MI) in mice and hypoxic cardiomyocytes in vitro. Mechanically, mild hypoxia prompted metabolic reprogramming which motivated cardiomyocyte proliferation by alleviating reactive oxygen species (ROS), while severe hypoxia coincided with oxidative stress that induced cardiomyocyte cell cycle arrest. Interestingly, LDHA nuclear translocation in cardiomyocytes occurred in response to oxidative stress, and blocking of nuclear LDHA resulted in elevated ROS generation. Collectively, our findings uncover a non-canonical role of nuclear LDHA in maintaining redox balance and resisting cardiomyocyte cell cycle arrest. Full article

To investigate the remediation efficiency of different plant species on cadmium (Cd)-contaminated soil, this study conducted a pot experiment with two woody species (Populu adenopoda and Salix babylonica) and two herbaceous species (Artemisia argyi and Amaranthus hypochondriacus). Soils were collected from an abandoned coal mine and adjacent pristine natural areas within the dam-adjacent section of the Three Gorges Reservoir Area to establish three soil treatment groups: unpolluted soil (T1, 0.18 mg·kg⁻¹ Cd), a 1:1 mixture of contaminated and unpolluted soil (T2, 0.35 mg·kg⁻¹ Cd), and contaminated coal mine soil (T3, 0.54 mg·kg⁻¹ Cd). This study aimed to investigate the growth status of plants, Cd accumulation and translocation characteristics, and the relationship between them and soil environmental factors. Woody plants exhibited significant advantages in aboveground biomass accumulation. Under T3 treatment, the Cd extraction amount of S. babylonica (224.93 mg) increased by about 36 times compared to T1, and the extraction efficiency (6.42%) was significantly higher than other species. Among the herbaceous species, A. argyi showed the maximum Cd extraction amount (66.26 mg) and extraction efficiency (3.11%) during T2 treatment. While A. hypochondriacus exhibited a trend of increasing extraction amount but decreasing extraction efficiency with increasing concentration. With the exception of S. babylonica under T1 treatment (BCF = 0.78), the bioconcentration factor was greater than 1 in both woody (BCF = 1.39–6.42) and herbaceous species (BCF = 1.39–3.11). However, herbaceous plants demonstrated significantly higher translocation factors (TF = 1.58–3.43) compared to woody species (TF = 0.31–0.87). There was a significant negative correlation between aboveground phosphorus (P) content and root Cd (p < 0.05), while underground nitrogen (N) content was positively correlated to aboveground Cd content (p < 0.05). Soil total N and available P were significantly positively correlated with plant Cd absorption, whereas total potassium (K) showed a negative correlation. This study demonstrated that woody plants can achieve long-term remediation through biomass advantages, while herbaceous plants, with their high transfer efficiency, are suitable for short-term rotation. In the future, it is suggested to conduct a mixed planting model of woody and herbaceous plants to remediate Cd-contaminated soils in the tailing areas of reservoir areas. This would synergistically leverage the dual advantages of root retention and aboveground removal, enhancing remediation efficiency. Concurrent optimization of soil nutrient management would further improve the Cd remediation efficiency of plants. Full article

Deciphering the spatiotemporal distribution of bacteria during breast cancer progression may provide critical insights for developing bacterial-based therapeutic strategies. Using a murine breast cancer model, we longitudinally profiled the microbiota in breast tumor tissue, mammary gland, spleen, and cecal contents at 3-, 5-, and 7- weeks post-tumor implantation through 16S rRNA gene sequencing. Breast tumor progression was associated with lung metastasis and splenomegaly, accompanied by distinct tissue-specific microbial dynamics. While alpha diversity remained stable in tumors, mammary tissue, and cecal contents, it significantly increased in the spleen (p < 0.05). Longitudinal analysis revealed a progressive rise in Firmicutes and a decline in Proteobacteria abundance within tumors, mammary tissue, and cecum, whereas the spleen microbiota displayed unique phylum-level compositional shifts. Tissue- and time-dependent microbial signatures were identified at phylum, genus, and species levels during breast tumor progression. Strikingly, the spleen microbiota integrated nearly all genera enriched in other sites, suggesting its potential role as a microbial reservoir. Gut-associated genera (Lactobacillus, Desulfovibrio, Helicobacter) colonized both cecal contents and the spleen, with Lactobacillus consistently detected across all tissues, suggesting microbial translocation. The spleen exhibited uniquely elevated diversity and compositional shifts, potentially driving splenomegaly. These results delineated the trajectory of microbiota translocation and colonization, and demonstrated tissue-specific microbial redistribution during breast tumorigenesis, offering valuable implications for advancing microbiome-targeted cancer therapies. Full article

The NADPH oxidase 2 (NOX2) complex is a critical regulator of immune homeostasis. It is utilized by phagocytic leukocytes including neutrophils, monocytes, and macrophages to generate reactive oxygen species (ROS) that drive microbe clearance and modulate inflammatory responses. Within NOX2, the essential scaffold protein p47phox plays a pivotal role in orchestrating enzyme activation and facilitating the assembly and membrane translocation of cytosolic components of the complex. Tight regulation of p47phox activity is crucial, and its disruption is linked to a number of pathological conditions. Conversely, its hyperactivity contributes to oxidative stress, tissue damage, the progression of cardiovascular diseases, neurodegenerative disorders, inflammatory conditions, metabolic syndromes, and cancer. In this review, we detail the structural and functional roles of p47phox, mechanisms of its regulation, and its multifaceted contributions to disease pathogenesis. We explore the latest advances in p47phox-targeted therapeutic strategies, discuss current challenges in the field, highlight p47phox’s potential as a transformative target in redox biology and propose future directions to unlock its clinical utility. Full article

Phytoremediation is based on the use of plants to decontaminate water and soil. In this work, the capacity of high Andean vegetation in the absorption and translocation of heavy metals was analyzed. Species were identified to analyze the presence of metals in roots, stems, and leaves by spectrometry. The translocation factor was determined and analyzed by means of pattern clusters. Based on the floristic inventory, the dominance of the Poaceae and Asteraceae families was determined, and 12 plant species with a high importance value were selected. According to the ICP-AES, mercury (951.07 mg/kg) was determined in the roots of Lachemilla orbiculata, and chromium (21.88 mg/kg) in Carex bonplandii. Arsenic (2.79 mg/kg) was detected as being significantly higher than the values recorded in lowland plants. Cadmium mobility was high in all species, reaching higher values in Baccharis salicifolia (86.28%) and Calamagrostis intermedia (37.16%). Rumex acetocella accumulated lead in leaves (9.27%), while Taraxacum officinale (1.20%) and Calamagrostis intermedia (1.20%) accumulated silicon. Stabilization of chromium, mercury, and sodium was determined in the roots without translocation to higher organs. Finally, cluster analysis showed physiological interactions between metals as a toxicity mitigation mechanism affecting mobility. These findings suggest that they are hyperaccumulator species. Full article

We have previously shown that the mitochondrial respiratory chain (RC) can switch between the following two states: (i) an “ATP-producing” state characterized by the low production of reactive oxygen species (ROS), the vigorous translocation of hydrogen ions (H⁺), and the storage of energy from the H⁺ gradient in the form of ATP, and (ii) an “ROS-producing” state, where the translocation of H⁺ is slow but the production of ROS is high. Here, we suggest that the RC transition from an ATP-producing to an ROS-producing state initiates a mitochondrial permeability transition (MPT) by generating a burst of ROS. Numerous MPT activators induce the transition of the RC to an ROS-producing state, and the ROS generated in this state activate the MPT. The MPT, in turn, induces changes in conditions that are necessary for the RC to return to an ATP-producing state, decreasing the ROS production rate and restoring the normal permeability of the inner membrane. In this way, the transient MPT prevents cell damage from oxidative stress that would occur if the RC remained in an ROS-producing state. It is shown that an overload of glutamate, which enters through excitatory amino acid transporters (EAATs), induces the RC to switch to an ROS-producing state. Subsequent MPT activation causes a transition back to an ATP-producing state. The model was used to predict the spatial–temporal dynamics of glutamate concentrations and H₂O₂ production rates in a three-dimensional digital phantom of nervous tissue. Full article

Edge populations can harbor unique genetic diversity shaped by historical isolation and play a key role in species’ resilience and range expansion under ongoing climate warming. The Aesculapian snake (Zamenis longissimus) reaches the northern limit of its range in Central Europe, where isolated populations may provide key insights into the species’ evolutionary potential and conservation priorities. In Bohemia (the western Czech Republic), only one reproducing population, in the vicinity of Stráž nad Ohří (SO), had previously been confirmed north of the species’ continuous distribution. Here, we report two additional reproducing populations recently discovered through long-term monitoring: one at the Želinský meander (ZM) and another in Central Bohemia (CB). The ZM population is autochthonous, viable, and genetically remarkable, harboring two divergent mitochondrial haplotypes: the widespread Eastern phylogeographical clade haplotype E1 and a novel haplotype, W10, belonging to the Western clade. This represents the first confirmed record of a Western clade haplotype in the Czech Republic, and only the second known locality within the species’ entire range where both clades coexist. In contrast, the CB population—founded by human-mediated translocation from SO—is expanding dynamically and is represented solely by E1, the only haplotype previously recorded in the country. Our study highlights the importance of incorporating genetic data into conservation planning and understanding species’ evolutionary potential. The mitochondrial diversity uncovered at the ZM exemplifies how historical processes, isolation, and lineage mixing shape contemporary genetic structure. Preserving such populations, which retain unique evolutionary diversity, will be critical for maintaining the resilience of Z. longissimus in Central Europe. More broadly, disjunct northern populations may serve as reservoirs of genetic diversity, enhancing adaptive potential and supporting future range expansion under climate change. Recognizing and conserving this diversity is essential not only for local persistence but also for species-level resilience in a rapidly changing environment. Full article

Cardioprotection against ischemia is achieved using openers of mitochondrial ATP-sensitive K⁺ (mitoKATP) channels such as diazoxide (DZX), leading to pharmacological preconditioning (PPC). We previously reported that PPC decreases the abundance of ventricular Cav1.2 channels, but PPC’s effects on other channels remain largely unexplored. In this study, we hypothesized that DZX regulates the expression of hyperpolarization-activated cyclic nucleotide potassium channel 4 (HCN4) channels in sinoatrial node cells (SANCs), the specialized cardiomyocytes that generate the heartbeat. DZX increased the heart rate in intact adult rats. Patch-clamp experiments revealed an increase in the magnitude of ionic currents through HCN4 channels, which was abolished by the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the selective mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assays showed that DZX increased HCN4 channel expression at the mRNA and protein levels. Immunofluorescence analyses revealed that PPC increased HCN4 fluorescence, which was abolished by NAC. DZX increased nuclear translocation of c-Fos and decreased protein abundance of RE1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), suggesting the involvement of these factors. Our results suggest that PPC increases the heart rate by upregulating HCN4 channel expression through a mechanism involving c-Fos, REST, and ROS. Full article