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This article discusses the importance of redox regulation in plant growth and adaptation to environmental conditions. Redox regulation, which involves the exchange of electrons, is essential for energy conversion and is also used to regulate physiological processes in plants. The article highlights the complexity of redox regulation, which extends beyond photosynthesis to various subcellular compartments. It also discusses the role of reactive oxygen species (ROS) and nitric oxide (NO) as signaling molecules in plant defense and stress responses. The article emphasizes the need for further research to understand the functional impact of redox modifications on protein structure and function, and suggests that advancements in technology and artificial intelligence (AI) will play a crucial role in this research. [Extracted from the article]

Reactive Oxygen Species (ROS) can be harmful compounds that can cause damage to macromolecules like lipids, proteins, and DNA when their levels exceed cellular defense mechanisms. Cells have protection and ROS detoxification systems, including thioredoxin and glutaredoxin systems, to counteract oxidative stress. The role of cytosolic thioredoxin system (cTRX) was investigated in different growth phases using a mutant strain lacking both TRX1 and TRX2. The mutant showed a defect in survival during the non-dividing state or stationary phase. The levels of glutathione, an antioxidant, in the mutants were higher in both total and reduced glutathione, indicating an increase in oxidative response. The mutant also showed an increase in protein-bound glutathione, suggesting a compensatory mechanism to counter balance oxidative stress. Proteomic analysis revealed changes in the expression of various proteins in the absence of cytosolic thioredoxins. Upregulated proteins in both exponential and stationary phases were mainly related to oxidative stress response and metabolism. Downregulated proteins in both phases were associated with glycerol metabolism, glycolysis, and ATP synthesis. These changes indicated a compensatory response to redox imbalance caused by the absence of cytosolic thioredoxins. Further analysis focused on the reversible oxidation of cysteine residues in proteins. Several proteins were identified with cysteines susceptible to reversible oxidation, and their oxidation status was affected by the absence of cytosolic thioredoxins. Notably, cysteine 146 of cytosolic Superoxide Dismutase 1 (Sod1) was more oxidized in growth phase, while oxidation of ribosomal proteins was seen only in exponential phase.Overall, this study provides insights into the role of cytosolic thioredoxin system in growth, aging, in maintaining redox balance, protecting against oxidative stress as well as its impact on SOD1 activity and glutathionylation.

Reactive Oxygen Species (ROS) and mitochondrial dysfunction are implicated in the pathogenesis of Alzheimer's disease (AD), a common neurodegenerative disorder characterized by abnormal metabolism of the amyloid precursor protein (APP) in brain tissue. However, the exact mechanism by which abnormal APP leads to oxidative distress remains unclear. Damage to mitochondrial membrane and inhibition of mitochondrial respiration are thought to contribute to the progression of the disease. However, the lack of suitable human models that replicate pathological features, together with impaired cellular pathways, constitutes a major challenge in AD studies. In this work, we induced pluripotency in patient-derived skin fibroblasts carrying the Swedish mutation in App (APPswe), to generate human brain organoids that model AD, and studied redox regulation and mitochondrial homeostasis. We found time-dependent increases in AD-related pathological hallmarks in APPswe brain organoids, including elevated Aβ levels, increased extracellular amyloid deposits, and enhanced tau phosphorylation. Interestingly, using live-imaging spinning-disk confocal microscopy, we found an increase in mitochondrial fragmentation and a significant loss of mitochondrial membrane potential in APPswe brain organoids when subjected to oxidative conditions. Moreover, ratiometric dyes in a live imaging setting revealed a selective increase in mitochondrial superoxide anion and hydrogen peroxide levels in APPswe brain organoids that were coupled to impairments in cytosolic and mitochondrial redoxin protein expression. Our results suggest a selective increase in mitochondrial vulnerability to oxidative conditions in APPswe organoids, indicating that the abnormal metabolism of APP leads to specific changes in mitochondrial homeostasis that enhance the vulnerability to oxidation in AD. [Display omitted] • We develop a human brain model that exhibit pathological hallmarks of Alzheimer's disease. • APPswe mutation induces mitochondrial-derived oxidative distress in human brain organoids. • Mitochondrial vulnerability to oxidation is exacerbated in a human model of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Periodontitis is a multifactorial and infective oral disease that leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, exploring new therapeutic strategies for a personalized approach is urgent. For this reason, the aim of this study is to summarize recent advances and the potential of oxidative stress biomarkers in the early diagnosis and personalized therapeutic approaches in periodontitis. Recently, ROS metabolisms (ROMs) have been studied in the physiopathology of periodontitis. Different studies show that ROS plays a crucial role in periodontitis. In this regard, the reactive oxygen metabolites (ROMs) started to be searched for the measures of the oxidizing capacity of the plasma understood as the total content of oxygen free radicals (ROS). The oxidizing capacity of plasma is a significant indicator of the body's oxidant state as well as homocysteine (Hcy), sulfur amino acid, which has pro-oxidant effects as it favors the production of superoxide anion. More specifically, the thioredoxin (TRX) and peroxiredoxin (PRX) systems control reactive oxygen species (ROS), such as superoxide and hydroxyl species, to transduce redox signals and change the activities of antioxidant enzymes to remove free radicals. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), among other antioxidant enzymes, change their activity when ROS are produced in order to neutralize free radicals. The TRX system is triggered and transduces redox signals to do this. [ABSTRACT FROM AUTHOR]

Thioredoxins (Trx) are small multifunctional redox proteins that contain thioredoxin conserved domain and active site WCXXC. The Trx family has an important role in multiple processes, including electron transport, seed germination, redox regulation, biotic and abiotic stresses resistance, etc. Although Trx genes have been extensively characterized in some plants, they have not been reported in peanut until now. The identification of AhTrx genes provides potential candidate genes for studying their effects and regulatory mechanisms in peanut (Arachis hypogaea L.) growth and development, especially under aluminium (Al) stress. It is also helpful to further analyze the Al resistance pathway in plants. Seventy AhTrx genes were identified using a genome-wide search method and conservative domain analysis. Then the basic physicochemical properties, phylogenetic relationship, gene structure, chromosomal localization, and promoter prediction were studied by the bioinformatic methods. Furthermore, the expressions of AhTrx genes under different Al treatment times in two peanut cultivars were tested using a real-time quantitative polymerase chain reaction. Seventy AhTrx genes were identified and characterized. Phylogenetic tree analysis showed that all AhTrx members could be classified into 9 groups with different conserved domains. Motif 1 was found to exist in every sequence, with an active site. Furthermore, the gene structures showed that the AhTrx family was complicated and changeable during evolution. The chromosomal localization indicated that the distribution and density of the Trx family on 20 peanut chromosomes were uneven. Predictive promoter analysis indicated that AhTrx proteins might play a role in phytohormones synthesis and stress response. Finally, the expression patterns of the AhTrx genes showed that every gene was differently expressed under Al treatment in different peanut cultivars, some were obvious, others had no significant difference, some were at a high level, while others were at a low level. This study systematically identifies the Trx gene family in peanut, providing some candidates for further study on its effects and regulatory mechanism under Al stress in peanut. [ABSTRACT FROM AUTHOR]

Thioredoxins (Trx) are small multifunctional redox proteins that contain thioredoxin conserved domain and active site WCXXC. The Trx family has an important role in multiple processes, including electron transport, seed germination, redox regulation, biotic and abiotic stresses resistance, etc. Although Trx genes have been extensively characterized in some plants, they have not been reported in peanut until now. The identification of AhTrx genes provides potential candidate genes for studying their effects and regulatory mechanisms in peanut (Arachis hypogaea L.) growth and development, especially under aluminium (Al) stress. It is also helpful to further analyze the Al resistance pathway in plants. Seventy AhTrx genes were identified using a genome-wide search method and conservative domain analysis. Then the basic physicochemical properties, phylogenetic relationship, gene structure, chromosomal localization, and promoter prediction were studied by the bioinformatic methods. Furthermore, the expressions of AhTrx genes under different Al treatment times in two peanut cultivars were tested using a real-time quantitative polymerase chain reaction. Seventy AhTrx genes were identified and characterized. Phylogenetic tree analysis showed that all AhTrx members could be classified into 9 groups with different conserved domains. Motif 1 was found to exist in every sequence, with an active site. Furthermore, the gene structures showed that the AhTrx family was complicated and changeable during evolution. The chromosomal localization indicated that the distribution and density of the Trx family on 20 peanut chromosomes were uneven. Predictive promoter analysis indicated that AhTrx proteins might play a role in phytohormones synthesis and stress response. Finally, the expression patterns of the AhTrx genes showed that every gene was differently expressed under Al treatment in different peanut cultivars, some were obvious, others had no significant difference, some were at a high level, while others were at a low level. This study systematically identifies the Trx gene family in peanut, providing some candidates for further study on its effects and regulatory mechanism under Al stress in peanut.

Photosynthetic light reactions require strict regulation under dynamic environmental conditions. Still, depending on environmental constraints, photoinhibition of Photosystem (PSII) or PSI occurs frequently. Repair of photodamaged PSI, in sharp contrast to that of PSII, is extremely slow and leads to a functional imbalance between the photosystems. Slow PSI recovery prompted us to take advantage of the PSI‐specific photoinhibition treatment and investigate whether the imbalance between functional PSII and PSI leads to acclimation of photosynthesis to PSI‐limited conditions, either by short‐term or long‐term acclimation mechanisms as tested immediately after the photoinhibition treatment or after 24 h recovery in growth conditions, respectively. Short‐term acclimation mechanisms were induced directly upon inhibition, including thylakoid protein phosphorylation that redirects excitation energy to PSI as well as changes in the feedback regulation of photosynthesis, which relaxed photosynthetic control and excitation energy quenching. Longer‐term acclimation comprised reprogramming of the stromal redox system and an increase in ATP synthase and Cytochrome b6f abundance. Acclimation to PSI‐limited conditions restored the CO2 assimilation capacity of plants without major PSI repair. Response to PSI inhibition demonstrates that plants efficiently acclimate to changes occurring in the photosynthetic apparatus, which is likely a crucial component in plant acclimation to adverse environmental conditions. [ABSTRACT FROM AUTHOR]

Thioredoxins (Trxs) and Glutaredoxins (Grxs) regulate several cellular processes by controlling the redox state of their target proteins. Trxs and Grxs belong to thioredoxin superfamily and possess characteristic Trx/Grx fold. Several phylogenetic, biochemical and structural studies have contributed to our overall understanding of Trxs and Grxs. However, comparative study of closely related Trxs and Grxs in organisms of all domains of life was missing. Here, we conducted in silico comparative structural analysis combined with amino acid sequence and phylogenetic analyses of 65 Trxs and 88 Grxs from 12 organisms of three domains of life to get insights into evolutionary and structural relationship of two proteins. Outcomes suggested that despite diversity in their amino acids composition in distantly related organisms, both Trxs and Grxs strictly conserved functionally and structurally important residues. Also, position of these residues was highly conserved in all studied Trxs and Grxs. Notably, if any substitution occurred during evolution, preference was given to amino acids having similar chemical properties. Trxs and Grxs were found more different in eukaryotes than prokaryotes due to altered helical conformation. The surface of Trxs was negatively charged, while Grxs surface was positively charged, however, the active site was constituted by uncharged amino acids in both proteins. Also, phylogenetic analysis of Trxs and Grxs in three domains of life supported endosymbiotic origins of chloroplast and mitochondria, and suggested their usefulness in molecular systematics. We also report previously unknown catalytic motifs of two proteins, and discuss in detail about effect of abovementioned parameters on overall structural and functional diversity of Trxs and Grxs.

SUMMARY: Reactive oxygen species (ROS) such as singlet oxygen, superoxide (O2●−) and hydrogen peroxide (H2O2) are the markers of living cells. Oxygenic photosynthesis produces ROS in abundance, which act as a readout of a functional electron transport system and metabolism. The concept that photosynthetic ROS production is a major driving force in chloroplast to nucleus retrograde signalling is embedded in the literature, as is the role of chloroplasts as environmental sensors. The different complexes and components of the photosynthetic electron transport chain (PETC) regulate O2●− production in relation to light energy availability and the redox state of the stromal Cys‐based redox systems. All of the ROS generated in chloroplasts have the potential to act as signals and there are many sulphhydryl‐containing proteins and peptides in chloroplasts that have the potential to act as H2O2 sensors and function in signal transduction. While ROS may directly move out of the chloroplasts to other cellular compartments, ROS signalling pathways can only be triggered if appropriate ROS‐sensing proteins are present at or near the site of ROS production. Chloroplast antioxidant systems serve either to propagate these signals or to remove excess ROS that cannot effectively be harnessed in signalling. The key challenge is to understand how regulated ROS delivery from the PETC to the Cys‐based redox machinery is organised to transmit redox signals from the environment to the nucleus. Redox changes associated with stromal carbohydrate metabolism also play a key role in chloroplast signalling pathways. [ABSTRACT FROM AUTHOR]

Thioredoxins are oxidoreductases that help to maintain redox homeostasis in plants under abiotic stress. In this study, a new thioredoxin gene, SikTrxh, was cloned from Saussurea involucrata (Kar. & Kir.), a perennial herb that grows in the high alpine mountains of Central Asia. Bioinformatics analysis shows that the full-length cDNA of SikTrxh consisted of 565 bp with a 354-bp open reading frame and encoded a 117 amino acid protein. Using quantitative reverse transcription (RT) PCR, we found that the expression of the SikTrxh gene was induced by salt, cold, and drought stresses, suggesting that this protein played a significant role in plant defense. Subcellular localization confirmed that the protein was localized to the mitochondria. A vector carrying SikTrxh was inserted into tobacco, and successfully modified plants were identified by RT-PCR. Physiological indicators and antioxidant enzyme activities were measured under low temperature, and salt and drought stresses. Our results show that malondialdehyde content and relative electrolyte leakage increased in both wild-type and SikTrxh-overexpressing transgenic plants; however, these increases were significantly higher in the wild-type plants than in the transgenic plants. We also found that photosystem II photoinhibition was lower in the transgenic plants than in the wild-type plants, and that activities of reactive oxygen species-scavenging enzymes were higher in the transgenic plants than in the wild-type plants. We conclude that SikTrxh can reduce toxic effects of reactive oxygen species to protect the plasma membrane, thereby increasing plant resistance to abiotic stresses.

Genetically-encoded redox biosensors have become invaluable tools for monitoring cellular redox processes with high spatiotemporal resolution, coupling the presence of the redox-active analyte with a change in fluorescence signal that can be easily recorded. This review summarizes the available fluorescence recording methods and presents an in-depth classification of the redox biosensors, organized by the analytes they respond to. In addition to the fluorescent protein-based architectures, this review also describes the recent advances on fluorescent, chemigenetic-based redox biosensors and other emerging chemigenetic strategies. This review examines how these biosensors are designed, the biosensors sensing mechanism, and their practical advantages and disadvantages. [Display omitted] • Fluorescent tools that monitor cellular redox metabolites in situ and in real time. • Different fluorescence recording modalities (intensity, lifetime, anisotropy). • Available biosensors to monitor cellular GSH/GSSG, hydrogen peroxide, NADH, NADPH. • Description of biosensors architecture, properties and limitations. • Novel biosensor architectures that use chemigenetic reporters: HaloTag, UnaG, FAST. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are essential regulators of plant growth, development and defense. The regulated compartment-specific production and processing of ROS are central to the reduction-oxidation (redox) balance of the intracellular and extracellular environments. ROS generation has often been considered to be harmful, because of the potential collateral damage, but their high chemical reactivity is essential to their roles as pro-life signals. Nevertheless, literature evidence demonstrates that the ability to mount a robust antioxidant defense is integral to stress tolerance in soybean as in other plant species. Moreover, the integration of redox signaling with reactive nitrogen species and molecular oxygen signaling is crucial to the functioning of many plant organs, such as seeds and nodules, which are maintained in a state of developmental hypoxia. Here, we describe ROS production, processing and signaling in soybean, particularly in relation to nodule development and protection against environmental stresses. We also consider the interactions between ROS and nitric oxide (NO), highlighting gaps in current knowledge and considering future research directions in exploring redox metabolism in soybean. [ABSTRACT FROM AUTHOR]

Bacilliredoxins are small proteins that are involved in redox homeostasis in bacillithiol‐producing bacteria. They reduce mixed bacillithiol disulfides on protected proteins through a disulfide‐exchange reaction, restoring the thiol group on the target protein. Bacilliredoxins contain an unusual conserved CGC motif, and their exact catalytic mechanism remains unclear. Here, a 1.6 Å resolution X‐ray crystallographic structure of the bacilliredoxin BrxA (YphP) from Staphylococcus aureus is presented. The structure contains bacillithiol in a mixed disulfide with Cys54, as well as a disulfide linkage at Cys56, which may play a role in dimer stabilization. The structure presented here will provide insight into the function of BrxA and other bacilliredoxins. [ABSTRACT FROM AUTHOR]

Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood. In this study, we found that TXNIP knockout suppressed renal fibrosis and activation of mammalian target of rapamycin complex 1 (mTORC1) and restored transcription factor EB (TFEB) and autophagy activation in diabetic kidneys. Simultaneously, TXNIP interference inhibited epithelial-to-mesenchymal transformation (EMT), collagen I and fibronectin expression, and mTORC1 activation, increased TFEB nuclear translocation, and promoted autophagy restoration in HK-2 cells exposed to high glucose (HG). Rapamycin, an inhibitor of mTORC1, increased TFEB nuclear translocation and autophagy in HK-2 cells under HG conditions. Moreover, the TFEB activators, curcumin analog C1 and trehalose, effectively restored HG-induced autophagy, and abrogated HG-induced EMT and collagen I and fibronectin expression in HK-2 cells. Taken together, these findings suggest that TXNIP deficiency ameliorates renal fibrosis by regulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseases.

Thioredoxins (Trx) are small multifunctional redox proteins that contain thioredoxin conserved domain and active site WCXXC. The Trx family has an important role in multiple processes, including electron transport, seed germination, redox regulation, biotic and abiotic stresses resistance, etc. Although Trx genes have been extensively characterized in some plants, they have not been reported in peanut until now. The identification of AhTrx genes provides potential candidate genes for studying their effects and regulatory mechanisms in peanut (Arachis hypogaea L.) growth and development, especially under aluminium (Al) stress. It is also helpful to further analyze the Al resistance pathway in plants. Seventy AhTrx genes were identified using a genome-wide search method and conservative domain analysis. Then the basic physicochemical properties, phylogenetic relationship, gene structure, chromosomal localization, and promoter prediction were studied by the bioinformatic methods. Furthermore, the expressions of AhTrx genes under different Al treatment times in two peanut cultivars were tested using a real-time quantitative polymerase chain reaction. Seventy AhTrx genes were identified and characterized. Phylogenetic tree analysis showed that all AhTrx members could be classified into 9 groups with different conserved domains. Motif 1 was found to exist in every sequence, with an active site. Furthermore, the gene structures showed that the AhTrx family was complicated and changeable during evolution. The chromosomal localization indicated that the distribution and density of the Trx family on 20 peanut chromosomes were uneven. Predictive promoter analysis indicated that AhTrx proteins might play a role in phytohormones synthesis and stress response. Finally, the expression patterns of the AhTrx genes showed that every gene was differently expressed under Al treatment in different peanut cultivars, some were obvious, others had no significant difference, some were at a high level, while others were at a low level. This study systematically identifies the Trx gene family in peanut, providing some candidates for further study on its effects and regulatory mechanism under Al stress in peanut. [ABSTRACT FROM AUTHOR]

Thiol-based redox compounds, namely thioredoxins (Trxs), glutaredoxins (Grxs) and peroxiredoxins (Prxs), stand as a pivotal group of proteins involved in antioxidant processes and redox signaling. Glutaredoxins (Grxs) are considered as one of the major families of proteins involved in redox regulation by removal of S-glutathionylation and thereby reactivation of other enzymes with thiol-dependent activity. Grxs are also coupled to Trxs and Prxs recycling and thereby indirectly contribute to reactive oxygen species (ROS) detoxification. Peroxiredoxins (Prxs) are a ubiquitous family of peroxidases, which play an essential role in the detoxification of hydrogen peroxide, aliphatic and aromatic hydroperoxides, and peroxynitrite. The Trxs, Grxs and Prxs systems, which reversibly induce thiol modifications, regulate redox signaling involved in various biological events in the cardiovascular system. This review focuses on the current knowledge of the role of Trxs, Grxs and Prxs on cardiovascular pathologies and especially in cardiac hypertrophy, ischemia/reperfusion (I/R) injury and heart failure as well as in the presence of cardiovascular risk factors, such as hypertension, hyperlipidemia, hyperglycemia and metabolic syndrome. Further studies on the roles of thiol-dependent redox systems in the cardiovascular system will support the development of novel protective and therapeutic strategies against cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: To explore the neuroprotective mechanism of artemisinin against ischemic stroke from the perspective of NLRP3-mediated pyroptosis., Methods: Serum metabolomics technology was used to analyze the serum samples of mice, and KEGG metabolic pathway was analyzed for the different metabolites in the samples. PIT model and OGD/R model were used to simulate ischemic stroke damage in vivo and in vitro. Hoechst 33342 staining, Annexin V-FITC/PI staining and TUNEL staining were used to detect the pyroptosis rate of cells. The contents of IL-1β and IL-18 in PC12 cells and serum of mice were detected by ELISA. The expressions of NLRP3, ASC-1, Caspase-1 and TXNIP in PC12 cells and mouse brain tissue were detected by Western Blot., Results: Serum metabolic profiles of animal models identified 234 different metabolites and 91 metabolic pathways. Compared with the Sham group and the Stroke+ART group, the KEGG pathway in the Stroke group was concentrated in the Necroptosis pathway associated with cell growth and death, and the NLRP3 inflammasome-mediated pyroptosis pathway was activated in the Necroptosis pathway after ischemic stroke. The results of in vivo and in vitro experiments showed that pretreatment with 10 μM artemisinin reduced ROS production, decreased Δψm, reduced pyroptosis, maintained neuronal cell morphology, and down-regulated the contents of IL-1β and IL-18 as well as the expression of key proteins of NLRP3, ASC-1, Caspase-1 and TXNIP(p<0.01)., Conclusion: Artemisinin can reduce neuronal pyroptosis induced by ischemic stroke by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1β (IL-1β) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1β, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species (ROS) and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial ROS., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Sinensetin (SIN), a polymethoxylated flavonoid, exists widely in citrus fruits with abundant biological activities, such as antioxidant and anti-inflammatory properties, delaying the progression of lung fibers and ameliorating inflammatory lung injury. Herein, an in vivo model of LPS-induced acute lung injury (ALI) in mice and an in vitro model of LPS + IFN-γ-induced M1 polarization in RAW264.7 cells were established to assess the effects and molecular mechanisms of SIN in ameliorating ALI. In the present study, the results showed that SIN significantly reduced BALF IL1β, IL6, and TNF-α levels and neutrophil infiltration, inhibited lung tissue COX2 and iNOS expression, reduced serum and lung tissue inflammatory factor levels, and attenuated lung tissue inflammatory infiltration and ROS levels in animal experiments. RNA sequencing analysis showed that SIN markedly inhibited the expression of inflammation-related pathway genes such as NOD-like receptor signaling. Further mechanistic studies confirmed that SIN significantly inhibited the dissociation of Txnip and Trx-1 and decreased the expression of NLRP3, ASC, pro-Caspase-1, cleavage Caspase-1 p10, NEK7, Caspase-8, IL1β, IL18, and GSDMD. Meanwhile, SIN docked to NLRP3 with strong affinity and bound stably in the hydrophobic docking pocket. Similarly, the same results were observed in in vitro macrophage M1 polarization experiments. In conclusion, the results revealed that SIN ameliorated the onset and progression of ALI by inhibiting Txnip/NLRP3/Caspase-1/GSDMD signaling-mediated inflammatory responses and pyroptosis. These findings emphasize the significant role of SIN in ameliorating ALI and provide insights into the strategy for exploring the functional effects of foods.

Background: Previous research has identified a significant role of Thioredoxin-interacting protein (TXNIP) in bone loss. The purpose of this investigation was to assess the role and the underlying molecular mechanisms of TXNIP in the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) and pre-osteoblast MC3T3-E1 cells., Methods: Human bone marrow stem cells (hBMSCs) and MC3T3-E1 cells were used to induce osteogenic differentiation. The expression of genes and proteins was assessed using RT-qPCR and western blot, respectively. ChIP assay was used to validate the interaction between genes. The osteogenic differentiation ability of cells was reflected using ALP staining and detection of ALP activity. The mineralization ability of cells was assessed using ARS staining. DCFCA staining was employed to evaluate the intracellular ROS level., Results: Initially, downregulation of TXNIP and upregulation of EZH2 were observed during osteogenesis in hBMSCs and MC3T3-E1 cells. Additionally, it was discovered that EZH2 negatively regulates TXNIP expression in these cells. Furthermore, experiments indicated that the knockdown of TXNIP stimulated the activation of the PI3K/AKT/Nrf2 signaling pathway in hBMSCs and MC3T3- E1 cells, thus inhibiting the production of reactive oxygen species (ROS). Further functional experiments revealed that overexpression of TXNIP inhibited the osteogenic differentiation in hBMSCs and MC3T3-E1 cells by enhancing ROS produc-tion. On the other hand, knockdown of TXNIP promoted the osteogenic differentiation capacity of hBMSCs and MC3T3-E1 cells through the activation of the PI3K/AKT/Nrf2 pathway., Conclusion: In conclusion, this study demonstrated that TXNIP expression, under the regulation of EZH2, plays a crucial role in the osteogenic differentiation of hBMSCs and MC3T3-E1 cells by regulating ROS production and the PI3K/AKT/Nrf2 pathway.

Diabetic liver injury (DLI) is one of the complications of diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and the mechanism needs to be further explored. In this study, a HFD/STZ-induced diabetic mouse model is established to investigate the effect and mechanism of PU on DLI. The results show that PU intervention significantly improves liver histology and serum biochemical abnormalities in diabetic mice, significantly inhibits the expression of pyroptosis-related proteins such as NLRP3, Caspase1, IL-1β, and GSDMD in the liver of diabetic mice, and up-regulated the expression of autophagy-related proteins. Meanwhile, PU treatment significantly increases FoxO1 protein expression and inhibits TXNIP protein expression in the liver of diabetic mice. The above results are further verified in the HepG2 cell injury model induced by high glucose. AS1842856 is a FoxO1 specific inhibitor. The intervention of AS1842856 combined with PU reverses the regulatory effects of PU on pyroptosis and autophagy in HepG2 cells. In conclusion, this study demonstrates that PU may inhibit pyroptosis and upregulate autophagy by regulating FoxO1/TXNIP signaling, thereby alleviating DLI., (© 2024 Wiley‐VCH GmbH.)

To improve the clinical outcome of adoptive NK cell therapy in patients with solid tumors, NK cells need to persist within the tumor microenvironment (TME) in which the abundance of ROS could dampen antitumor immune responses. In the present study, we demonstrated that IL-15-primed NK cells acquired resistance against oxidative stress through the thioredoxin system activated by mTOR. Mechanistically, the activation of thioredoxin showed dependence on localization of thioredoxininteracting protein. We show that NK cells residing in the tumor core expressed higher thiol densities that could aid in protecting other lymphocytes against ROS within the TME. Furthermore, the prognostic value of IL15 and the NK cell gene signature in tumors may be influenced by tobacco smoking history in patients with non-small-cell lung cancer (NSCLC). Collectively, the levels of reducing antioxidants in NK cells may not only predict better tumor penetrance but potentially even the immune therapy response., Introduction ROS are a diverse class of radical species that have different roles depending on their concentration. Considering their immune-suppressive effects, ROS have been proposed as a metabolic immune checkpoint [...]

Thioredoxins (TRXs), a large subclass of ubiquitous oxidoreductases, are involved in thiol redox regulation. Here, we performed a comprehensive analysis of TRXs in the Arabidopsis thaliana genome, revealing 41 genes encoding 18 typical and 23 atypical TRXs, and 6 genes encoding thioredoxin reductases (TRs). The high number of atypical TRXs indicates special functions in plants that mostly await elucidation. We identified an atypical class of thioredoxins called TRX‐c in the genomes of photosynthetic eukaryotes. Localized to the chloroplast, TRX‐c displays atypical CPLC, CHLC and CNLC motifs in the active sites. In silico analysis of the transcriptional regulations of TRXs revealed high expression of TRX‐c in leaves and strong regulation under cold, osmotic, salinity and metal ion stresses. [ABSTRACT FROM AUTHOR]

SUMMARY: Thioredoxins (TRXs) are well‐known redox signalling players, which carry out post‐translational modifications in target proteins. Chloroplast TRXs are divided into different types and have central roles in light energy uptake and the regulation of primary metabolism. The isoforms TRX m1, m2, and m4 from Arabidopsis thaliana are considered functionally related. Knowing their key position in the hub of plant metabolism, we hypothesized that the impairment of the TRX m signalling would not only have harmful consequences on chloroplast metabolism but also at different levels of plant development. To uncover the physiological and developmental processes that depend on TRX m signalling, we carried out a comprehensive study of Arabidopsis single, double, and triple mutants defective in the TRX m1, m2, and m4 proteins. As light and redox signalling are closely linked, we investigated the response to high light (HL) of the plants that are gradually compromised in TRX m signalling. We provide experimental evidence relating the lack of TRX m and the appearance of novel phenotypic features concerning mesophyll structure, stomata biogenesis, and stomatal conductance. We also report new data indicating that the isoforms of TRX m fine‐tune the response to HL, including the accumulation of the protective pigment anthocyanin. These results reveal novel signalling functions for the TRX m and underline their importance for plant growth and fulfilment of the acclimation/response to HL conditions. Significance Statement: Redox signalling mediated by the chloroplast m‐type thioredoxin regulates plant acclimation mechanisms in response to light intensity. The nature of the affected processes in Arabidopsis thaliana mutants deficient in the m‐type thioredoxin, grown at optimal and high light intensities, suggests that these proteins regulate, in an isoform‐dependent manner, important plant traits, so far unknown, which are beyond the regulation of the photosynthetic processes reported so far. [ABSTRACT FROM AUTHOR]

Objective: Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory disease, which is considered as a potentially malignant condition and could transformed into oral squamous cell carcinoma (OSCC). Squamous cell carcinmoma is the most common oral cancer. This study aimed to compare salivary thioredoxin levels as an antioxidant protein among patients with OSSC, OLP and healthy subjects. Materials and methods: Twenty‐eight patients with OLP, 20 patients with OSCC and 40 healthy people enrolled in this observational study. Saliva samples were collected from all subjects and salivary thioredoxin levels were evaluated by Elisa test. The data were recorded in the check lists and analyzed using SPSS (ver.17). Results: Thioredoxin levels of healthy controls were insignificantly higher than OLP and SCC patients (p = 0.135). There was a statistically remarkable indirect relationship between thioredoxin levels and severity of the lesions determined by Thongprasom criteria among OLP patients. The thioredoxin concentration was significantly higher in the keratotic OLP. Among the OSCC patients, the highest levels of thioredoxin were found among patients aged more than 65 years. Salivary thioredoxin levels based on other variables were not significantly different between the studied groups. Conclusion: In this study, there was not any significant difference between salivary thioredoxin levels in the OLP and OSCC patients, though it was unremarkable higher in the healthy group compared to the patients; therefore, the role of thioredoxin in the cellular oxidation–reduction status could be suggested; however, further studies are recommended. [ABSTRACT FROM AUTHOR]

Summary: Thioredoxins (TRXs) are ubiquitous disulfide oxidoreductases structured according to a highly conserved fold. TRXs are involved in a myriad of different processes through a common chemical mechanism. Plant TRXs evolved into seven types with diverse subcellular localization and distinct protein target selectivity. Five TRX types coexist in the chloroplast, with yet scarcely described specificities. We solved the crystal structure of a chloroplastic z‐type TRX, revealing a conserved TRX fold with an original electrostatic surface potential surrounding the redox site. This recognition surface is distinct from all other known TRX types from plant and non‐plant sources and is exclusively conserved in plant z‐type TRXs. We show that this electronegative surface endows thioredoxin z (TRXz) with a capacity to activate the photosynthetic Calvin–Benson cycle enzyme phosphoribulokinase. The distinct electronegative surface of TRXz thereby extends the repertoire of TRX–target recognitions. Significance Statement: The high‐resolution crystal structure of thioredoxin z (TRXz) from the model alga Chlamydomonas reinhardtii confirms that TRXz is generally structured as a canonical redox TRX but exposes a type‐specific electronegative surface around its active site. The ability of TRXz to interact with its target proteins is determined by this surface and reveals a compatibility with Calvin–Benson phosphoribulokinase that proved to be activated by TRXz in vitro. TRXz hence appears as a novel player in photosynthesis. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the leading cause of death worldwide and has in part an inflammatory basis. Since epicardial adipose tissue (EAT) is in close contact with coronary arteries we hypothesized that an imbalance in thioredoxin-1 (TRX-1) and thioredoxin interacting protein (TXNIP) in EAT, activates NLRP3 inflammasome and promotes production of IL-1β, leading to the development of atherosclerosis. Thirty-eight patients with coronary artery disease (CAD) and thirty patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as CAD and control groups, respectively. Biopsy samples from EAT were collected and expression of TXNIP, TRX-1, NLRP3 and IL-1β genes were assessed using qRT-PCR. Tissue protein levels of TXNIP and TRX-1 were determined by Western blotting while ELISA was applied to measure IL-1β. Haematoxylin and eosin staining was used for histological examination. mRNA and protein levels of TXNIP in EAT were significantly higher in patients with CAD compared with control group, whereas CAD patients showed lower TRX-1 gene and protein expression. In addition, in CAD patients the NLRP3 gene expression was almost doubled and IL-1β significantly increased at the both mRNA and protein levels. Enhancment in NLRP3 gene expression and TXNIP protein levels were accompanied with the increase in IL-1β protein level whereas TRX-1 protein content showed a negative correlation with IL-1β level. Concurrent increase in TXNIP, NLRP3, and IL-1β suggests possible involvement of thioredoxin system in the activation of NLRP3 inflammasome, production of IL-1β, and the presence of inflammation in CAD patients. [ABSTRACT FROM AUTHOR]