Search Results (1,070)

This survey reviews modern ideas on the structure and functions of mitochondrial and cytosolic aconitase isoenzymes in eukaryotes. Cumulative experimental evidence about mitochondrial aconitases (Aco2) as one of the main targets of reactive oxygen and nitrogen species is generalized. The important role of Aco2 in maintenance of homeostasis of the intracellular iron pool and maintenance of the mitochondrial DNA is discussed. The role of Aco2 in the pathogenesis of some neurodegenerative diseases is highlighted. Inactivation or dysfunction of Aco2 as well as mutations found in the ACO2 gene appear to be significant factors in the development and promotion of various types of neurodegenerative diseases. A restoration of efficient mitochondrial functioning as a source of energy for the cell by targeting Aco2 seems to be one of the promising therapeutic directions to minimize progressive neurodegenerative disorders. Full article

Oxidative stress is the result of the imbalance between reactive oxygen and nitrogen species (RONS), which are produced by several endogenous and exogenous processes, and antioxidant defenses consisting of exogenous and endogenous molecules that protect biological systems from free radical toxicity. Oxidative stress is a major factor in the aging process, contributing to the accumulation of cellular damage over time. Oxidative damage to cellular biomolecules, leads to DNA alterations, lipid peroxidation, protein oxidation, and mitochondrial dysfunction resulting in cellular senescence, immune system and tissue dysfunctions, and increased susceptibility to age-related pathologies, such as inflammatory disorders, cardiovascular and neurodegenerative diseases, diabetes, and cancer. Oxidative stress-driven DNA damage and mutations, or methylation and histone modification, which alter gene expression, are key determinants of tumor initiation, angiogenesis, metastasis, and therapy resistance. Accumulation of genetic and epigenetic damage, to which oxidative stress contributes, eventually leads to unrestrained cell proliferation, the inhibition of cell differentiation, and the evasion of cell death, providing favorable conditions for tumorigenesis. Colorectal, breast, lung, prostate, and skin cancers are the most frequent aging-associated malignancies, and oxidative stress is implicated in their pathogenesis and biological behavior. Our aim is to shed light on the molecular and cellular mechanisms that link oxidative stress, aging, and cancers, highlighting the impact of both RONS and antioxidants, provided by diet and exercise, on cellular senescence, immunity, and development of an antitumor response. The dual role of ROS as physiological regulators of cell signaling responsible for cell damage and diseases, as well as its use for anti-tumor therapeutic purposes, will also be discussed. Managing oxidative stress is crucial for promoting healthy aging and reducing the risk of age-related tumors. Full article

Vascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelial cells undergo an irreversible growth arrest and alter their functional state after a finite number of divisions, a phenomenon called replicative senescence. We assessed the contribution of NO during replicative senescence of human aortic (HAEC) and coronary (CAEC) endothelial cells, in which accumulation of the senescence marker SA-β-Gal was quantified by β-galactosidase staining on cultured cells. We found a negative correlation in passaged cell cultures from P0 to P12, between a reduction in NO production with increased ES and the formation of reactive oxygen (ROS) and nitrogen (ONOO⁻) species, indicative of oxidative and nitrosative stress. The effect of ES was evidenced by reduced expression of endothelial Nitric Oxide Synthase (eNOS), Interleukin Linked Kinase (ILK), and Heat shock protein 90 (Hsp90), alongside a significant increase in the BH2/BH4 ratio, inducing the uncoupling of eNOS, favoring the production of superoxide and peroxynitrite species, and fostering an inflammatory environment, as confirmed by the levels of Cyclophilin A (CypA) and its receptor Extracellular Matrix Metalloprotease Inducer (EMMPRIN). NO prevents ES by preventing the uncoupling of eNOS, in which oxidation of BH4, which plays a key role in eNOS producing NO, may play a critical role in launching the release of free radical species, triggering an aging-related inflammatory response. Full article

Drylands cover more than 40% of global land surface and will continue to expand by 10% at the end of this century. Understanding the resistance mechanisms of native species is of particular importance for vegetation restoration and management in drylands. In the present study, metabolome of a dominant shrub Campylotropis polyantha in a dry-hot valley were investigated. Compared to plants grown at the wetter site, C. polyantha tended to slow down carbon (C) assimilation to prevent water loss concurrent with low foliar reactive oxygen species and sugar concentrations at the drier and hotter site. Nitrogen (N) assimilation and turn over were stimulated under stressful conditions and higher leaf N content was kept at the expense of root N pools. At the drier site, roots contained more water but less N compounds derived from the citric acid cycle. The site had little effect on metabolites partitioning between leaves and roots. Generally, roots contained more C but less N. Aromatic compounds were differently impacted by site conditions. The present study, for the first time, uncovers the apparent metabolic adaptations of C. polyantha to hostile dryland conditions. However, due to the limited number of samples, we are cautious about drawing general conclusions regarding the resistance mechanisms. Further studies with a broader spatial range and larger time scale are therefore recommended to provide more robust information for vegetation restoration and management in dryland areas under a changing climate. Full article

Cys is one of the least abundant amino acids in proteins. However, it is often highly conserved and is usually found in important structural and functional regions of proteins. Its unique chemical properties allow it to undergo several post-translational modifications, many of which are mediated by reactive oxygen, nitrogen, sulfur, or carbonyl species. Thus, in addition to their role in catalysis, protein stability, and metal binding, Cys residues are crucial for the redox regulation of metabolism and signal transduction. In this review, we discuss Cys post-translational modifications (PTMs) and their role in plant metabolism and signal transduction. These modifications include the oxidation of the thiol group (S-sulfenylation, S-sulfinylation and S-sulfonylation), the formation of disulfide bridges, S-glutathionylation, persulfidation, S-cyanylation S-nitrosation, S-carbonylation, S-acylation, prenylation, CoAlation, and the formation of thiohemiacetal. For each of these PTMs, we discuss the origin of the modifier, the mechanisms involved in PTM, and their reversibility. Examples of the involvement of Cys PTMs in the modulation of protein structure, function, stability, and localization are presented to highlight their importance in the regulation of plant metabolic and signaling pathways. Full article

Nocturnal root and meristem temperature (RMT) can have a strong effect on rice growth and yield. However, underlying mechanisms are not well understood. To investigate the effects of night-time RMT on photosynthesis biomass allocation and activities of antioxidant enzymes, we designed a hydroponic system that maintained the following daily patterns of day/night temperature: 18/28 °C (HNT) or 28/18 °C (LNT). Rice plants cv. IR64 were grown in the greenhouse and subjected to either HNT or LNT. HNT stimulated growth and tillering but did not affect biomass allocation. HNT plants increased total biomass by 16 and 35%, depending on time of exposure. HNT increased rates of photosynthesis (Pn) compared to LNT plants in leaves of different ages. Overnight carbohydrate remobilisation was larger in HNT than in LNT plants, particularly at 16 days after treatment (dat), when Pn and relative growth rates were highest. Leaf soluble protein concentrations and specific leaf area were not affected by RMT, indicating higher photosynthetic nitrogen use efficiency in HNT plants. Super Oxide Dismutase, Ascorbate Peroxidase, and Glutathione Reductase activities did not respond to RMT, indicating no change in the production of reactive oxygen species in LNT plants despite lower photosynthesis rates. HNT increased sink demand by stimulating tillering, the increased sink demand upregulated the source activity through a larger leaf area per plant and a higher Pn throughout the canopy. The hydroponic system described here was able to control the temperature of the nutrient solution effectively, the installation of a second pump directly circulating the nutrient solution from and back to the reservoir through the cooling system allowed reaching the target temperature within 1 h. This system opens new opportunities to characterise plant responses to RMT alone or in combination with other environmental drivers. Full article

This study explores the potential of cold atmospheric plasma (CAP) to facilitate the delivery of large-molecule drugs to the brain. The blood–brain barrier (BBB) restricts the passage of most drugs, hindering treatment for neurological disorders. CAP generates reactive oxygen and nitrogen species (RONS) that may disrupt the BBB’s tight junctions, potentially increasing drug permeability. An in vitro BBB model and an immortalized cell line (bEND.3) were used in this experiment. Fluorescein isothiocyanate dextran (FD-4), a model drug, was added to the cells to determine drug permeability. Custom microplasma was used to produce reactive oxygen species (ROS). Trans-endothelial electrical resistance (TEER) measurements assessed the integrity of the BBB after the CAP treatment. A decrease in TEER was observed in the CAP-treated group compared to the controls, suggesting increased permeability. Additionally, fluorescence intensity measurements from the basal side of the trans-well plate indicated higher drug passage in the CAP-treated group. Moreover, the higher presence of ROS in the plasma-treated cells confirmed the potential of CAP in drug delivery. These findings suggest that CAP may be a promising approach for enhancing brain drug delivery. Full article

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder resulting from mutations in the NF1 gene. Patients harboring these mutations are predisposed to a spectrum of peripheral nerve sheath tumors (PNSTs) originating from Schwann cells, of which malignant peripheral nerve sheath tumors (MPNSTs) are the deadliest, with limited treatment options. Therefore, an unmet need still exists for more effective therapies directed at these aggressive malignancies. Cold atmospheric plasma (CAP) is a reactive oxygen species (ROS) and reactive nitrogen species (RNS) generating ionized gas that has been proposed to be a potential therapeutic modality for cancer. In this study, we sought to determine the effects of CAP on NF1-associated PNSTs. Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors. Full article

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain’s high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles. Full article

Gastroesophageal reflux disease (GERD) represents one of the most prevalent foregut illnesses, affecting a large portion of individuals worldwide. Recent research has shown that inflammatory mediators such as cytokines, chemokines, and enzymes are crucial for causing esophageal mucosa alterations in GERD patients. It seems likely that the expression of various cytokines in the esophageal mucosa also induces oxidative stress by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). As humoral agents and peptidergic neurotransmitters that may support the enterogastric axis, bombesin and its related bombesin-like peptide, GRP (gastrin releasing peptide), have not been fully investigated. Therefore, considering all these assumptions, this study aimed to evaluate the influence of bombesin in reestablishing biochemical markers linked with inflammation and oxidative/nitrosative stress in GERD pathological settings. C57BL/6 mice were alternatively overfed and fasted for 56 days to induce GERD and then treated with bombesin (0.1, 0.5, and 1 mg/kg intraperitoneally) once daily for 7 days, and omeprazole was used as the positive control. After 7 days of treatment, gastric pain and inflammatory markers were evaluated. Abdominal pain was significantly reduced following bombesin administration, which was also successful in diminishing inflammatory and oxidative/nitrosative stress markers in a manner overlapping with omeprazole. Moreover, bombesin was also able to appreciably modulate gastric pH as a result of the restoration of gastric homeostasis. Overall, these observations indicated that the upregulation of bombesin and interconnected peptides is a promising alternative approach to treat GERD patients. Full article

Cancer remains one of the leading causes of death despite advancements in research and treatment, with traditional therapies often causing significant side effects and resistance. Oxyhydrogen gas, a mixture of 66% molecular hydrogen (H₂) and 33% molecular oxygen (O₂) has shown exceptional promise as a novel therapeutic agent due to its ability to modulate oxidative stress, inflammation, and apoptosis. H₂, a key component of oxyhydrogen gas, neutralises reactive oxygen and nitrogen species, enhancing existing treatments and reducing harmful oxidative states in cancer cells. H₂ also lowers proinflammatory mediators including chemokines, cytokines, and interleukins, inhibiting cancer cell proliferation and boosting the effectiveness of conventional therapies. Additionally, hydrogen can induce apoptosis in cancer cells by modulating pathways such as MAPK and inhibiting the PI3K/Akt phosphorylation cascade. Preclinical and clinical evidence supports oxyhydrogen gas’s potential in treating various cancers. In lung cancer models, it inhibits cell proliferation, induces apoptosis, and enhances chemotherapy sensitivity. Similar results have been observed in breast cancer, where patients reported improved quality of life. In colorectal cancer, oxyhydrogen gas suppresses tumour growth, induces apoptosis, and improves intestinal microflora dysbiosis. The unique properties of oxyhydrogen gas make it a promising adjunctive or standalone cancer treatment. However, further research is needed to understand H₂s’ mechanisms, optimise treatment protocols, and evaluate long-term safety and efficacy in human patients. Full article

Cold atmospheric plasma (CAP) devices generate reactive oxygen and nitrogen species, have antimicrobial and antiviral properties, but also affect the molecular and cellular mechanisms of eukaryotic cells. The aim of this study is to investigate CAP treatment in the upper respiratory tract (URT) to reduce the incidence of ventilator-associated bacterial pneumonia (especially superinfections with multi-resistant pathogens) or viral infections (e.g., COVID-19). For this purpose, the surface-microdischarge-based plasma intensive care (PIC) device was developed by terraplasma medical GmbH. This study analyzes the safety aspects using in vitro assays and molecular characterization of human oral keratinocytes (hOK), human bronchial–tracheal epithelial cells (hBTE), and human lung fibroblasts (hLF). A 5 min CAP treatment with the PIC device at the “throat” and “subglottis” positions in the URT model did not show any significant differences from the untreated control (ctrl.) and the corresponding pressurized air (PA) treatment in terms of cell morphology, viability, apoptosis, DNA damage, and migration. However, pro-inflammatory cytokines (MCP-1, IL-6, and TNFα) were induced in hBTE and hOK cells and profibrotic molecules (collagen-I, FKBP10, and αSMA) in hLF at the mRNA level. The use of CAP in the oropharynx may make an important contribution to the recovery of intensive care patients. The results indicate that a 5 min CAP treatment in the URT with the PIC device does not cause any cell damage. The extent to which immune cell activation is induced and whether it has long-term effects on the organism need to be carefully examined in follow-up studies in vivo. Full article

Per-and Polyfluoroalkyl substances (PFASs) are recalcitrant organofluorine contaminants, which demand urgent attention due to their bioaccumulation potential and associated health risks. While numerous current treatments technologies, including certain plasma-based treatments, can degrade PFASs, their complete destruction or mineralization is seldom achieved. Extensive aqueous PFAS mineralization capability coupled with industrial-level scaling potential makes gliding arc plasma (GAP) discharges an interesting and promising technology in PFAS mitigation. In this study, the effects of GAP discharge’s thermal and reactive properties on aqueous perfluorooctanesulfonic acid (PFOS) mineralization were investigated. Treatments were conducted with air and nitrogen GAP discharges at different plasma gas temperatures to investigate the effects of plasma thermal environment on PFOS mineralization; the results show that treatments with increased plasma gas temperatures lead to increased PFOS mineralization, and discharges in air were able to mineralize PFOS at relatively lower plasma gas temperatures compared to discharges in nitrogen. Studies were conducted to identify if GAP-based PFOS mineralization is a pure thermal process or if plasma reactive chemistry also affects PFOS mineralization. This was done by comparing the effects of thermal environments with and without plasma species (air discharge and air heated to plasma gas temperatures) on PFOS mineralization; the results show that while GAP discharge was able to mineralize PFOS, equivalent temperature air without plasma did not lead to PFOS mineralization. Finally, mineralization during treatments with GAP discharges in argon and air at similar gas temperatures were compared to investigate the role of plasma species in PFOS mineralization. The results demonstrate that treatments with argon (monoatomic gas with higher ionization) lead to increased PFOS mineralization compared to treatments with air (molecular gas with lower ionization), showing the participation of reactive species in PFOS mineralization. Full article

In recent years, afforestation has been conducted in China’s hot and dry valleys. However, there is still a paucity of knowledge regarding the performance of tree species in these semi-arid regions, particularly with regard to interspecies differences. The present study compares the growth and metabolome characteristics of two widely used cypress species, namely Cupressus chengiana and Platycladus orientalis, grown at two sites with distinct climate conditions in the hot and dry Minjiang Valley in southwestern China. The findings indicate that C. chengiana trees exhibit superior growth rates compared to P. orientalis trees at both study sites. In comparison to P. orientalis trees, C. chengiana trees demonstrated a greater tendency to close their stomata in order to prevent water loss at the hotter and drier site, Llianghekou (LHK). Additionally, C. chengiana trees exhibited significantly lower hydrogen peroxide levels than P. orientalis trees, either due to lower production and/or higher scavenging of reactive oxygen species. C. chengiana trees accumulated soluble sugars as well as sugar derivatives, particularly those involved in sucrose and galactose metabolisms under stressful conditions. The species-specific differences were also reflected in metabolites involved in the tricarboxylic acid cycle, nitrogen, and secondary metabolisms. The metabolome profiles of the two species appeared to be influenced by the prevailing climatic conditions. It appeared that the trees at the drier and hotter site, LHK, were capable of efficient nitrogen uptake from the soil despite the low soil nitrogen concentration. This study is the first to compare the growth performance and metabolic profiles of two widely used tree species with high resistance to adverse conditions. In addition to the species-specific differences and adaptations to different sites, the present study also provides insights into potential management strategies to alleviate abiotic stress, particularly with regard to nitrogen nutrients, in the context of climate change. Full article

Fusarium graminearum, a devastating fungal pathogen, causes great economic losses to crop yields worldwide. The present study investigated the potential of Streptomyces pratensis S10 to alleviate F. graminearum stress in wheat seedlings based on plant growth-promoting and resistance-inducing assays. The bioassays revealed that S10 exhibited multiple plant growth-promoting properties, including the production of siderophores, 1-aminocyclopropane-1-carboxylic acid deaminase (ACC), and indole-3-acetic acid (IAA), phosphate solubilization, and nitrogen fixation. Meanwhile, the pot experiment demonstrated that S10 improved wheat plant development, substantially enhancing wheat height, weight, root activity, and chlorophyll content. Consistently, genome mining identified abundant genes associated with plant growth promotion. S10 induced resistance against F. graminearum in wheat seedlings. The disease incidence and disease index reduced by nearly 52% and 65% in S10 pretreated wheat seedlings, respectively, compared with those infected with F. graminearum only in the non-contact inoculation assay. Moreover, S10 enhanced callose deposition and reactive oxygen species (ROS) accumulation and induced the activities of CAT, SOD, POD, PAL, and PPO. Furthermore, the quantitative real-time PCR (qRT-PCR) results indicated that S10 pretreatment increased the expression of SA- (PR1.1, PR2, PR5, and PAL1) and JA/ET-related genes (PR3, PR4a, PR9, and PDF1.2) in wheat seedlings upon F. graminearum infection. In summary, S. pratensis S10 could be an integrated biological agent and biofertilizer in wheat seedling blight management and plant productivity enhancement. Full article