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At least 19 recordsLinked to original sources
PubMed2026

CaCl2 Priming Boosts Salinity-Alkalinity Tolerance in Germinating Soybean by Reducing DNA Oxidative Damage and Enhancing Ca2+ -ROS Signaling Crosstalk.

Soybean (Glycine max) seed germination is highly sensitive to saline-alkaline stress. Seed priming represents an effective strategy to mitigate its detrimental effects. However, the optimal priming conditions (agent, concentration, duration) and the underlying molecular mechanisms remain poorly understood. This study investigated the effects of priming with distilled water (Control), calcium chloride (CaCl2), melatonin (MT), and proline (Pro) under saline-alkaline stress on soybean seed germination and the molecular basis of enhanced tolerance. Evaluation of ten germination-related parameters revealed that priming with 100 mM CaCl2 for 12 h significantly enhanced the germination rate. Physiological analyses demonstrated that CaCl2 priming effectively reduced reactive oxygen species (ROS) accumulation by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), while decreasing malondialdehyde (MDA) content. Furthermore, CaCl2 priming activated the Ca2+ signaling pathway by increasing radicle Ca2+ content and upregulating the expression levels of Ca2+ signaling-related genes (e.g., GmCAM7, GmCNGC2, GmCNGC19, GmMPK2, and GmMKK2). Additionally, CaCl2 priming significantly enhanced DNA damage repair capacity of soybean cultivars with differing saline-alkaline tolerance. This was manifested by reduced DNA oxidative damage and decreased random amplified polymorphic DNA (RAPD) polymorphism, thereby enhancing genomic stability and alleviating cell cycle arrest. These findings deepen our understanding of the complex regulatory role of calcium signaling in plant abiotic stress responses and provide important novel theoretical insights for improving crop resilience.

Glycine max↗
PubMed2026

Functional impact of Nth like DNA glycosylase 1 on mitochondrial dynamics.

Nth like DNA glycosylase 1 (NTHL1), a key base excision repair enzyme, has long been considered essential for nuclear and mitochondrial genome integrity. Combining in vitro biochemical assays, in cellulo molecular biology, and bioinformatic analyses, we investigated how NTHL1 loss affects mitochondrial DNA (mtDNA) stability and mitochondrial function. Contrary to the conventional view that mtDNA damage is solely detrimental, we find that NTHL1 loss confers a beneficial, mitochondria-initiated phenotype in human cells. Despite accumulating mtDNA lesions, NTHL1 loss unexpectedly increases mtDNA copy number, elevates oxidative phosphorylation protein levels, and enhances mitochondrial respiration. NTHL1-/- cells also show increased mitochondrial mass and higher levels of the biogenesis regulator PGC1α and the fusion protein OPA1, indicating an adaptive response that boosts mitochondrial function and capacity. Consequently, NTHL1-/- cells exhibit resistance to mitochondrial stress, accompanied by increased eIF2α phosphorylation and reduced MYC levels, converging on a broader transcriptional adaptive program. This phenotype depends on mitochondrial NTHL1 and reactive oxygen species (ROS) signaling, since treatment with ROS scavengers or mitochondria-specific reintroduction of NTHL1 rescues it. Together, these findings position NTHL1 as a key modulator of mtDNA stability and mitochondrial function, revealing that loss of this DNA repair enzyme shifts cellular metabolism toward a stress-adaptive state and enhances resilience to oxidative stress.

Humans↗
PubMed2026

Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.

INTRODUCTION: R-loops, RNA-DNA hybrid structures with a displaced single-stranded DNA loop, are key regulators of transcriptional control, chromatin architecture, and genome stability and have emerging roles in inflammatory signaling. However, the relationship between R-loop abundance and strongly modulated inflammatory effector genes in metabolic inflammation and influenza virus infection remains underexplored. METHODS: We performed a locus-centric integrative analysis combining robust differentially expressed genes (DEGs) from multiple inflammatory and infection-related murine and human transcriptomic disease models with experimentally validated multi-cell R-loop annotations from the reference atlas RLoopBase. Our correlation framework evaluated the directional relationship between R-loop abundance and inflammatory gene expression rather than assuming disease-sample-matched R-loop measurements. We further analyzed R-loop regulatory proteins, NRF2-associated R-loop regulators, and overlaps between R-loop regulators and CRISPRi-identified mitochondrial and cellular reactive oxygen species (ROS) regulators. RESULTS: In angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice, a model of abdominal aortic aneurysm (AAA), genomic regions encoding the top significantly upregulated genes exhibited significantly fewer R-loops than those encoding downregulated genes at days 14 and 28. Similarly, in atherosclerotic ApoE-/- mice fed a high-fat diet for 32 and 78 weeks, upregulated genes were associated with fewer R-loops than downregulated genes. Reduced R-loop abundance was also observed in genomic regions encoding the top significantly upregulated genes in liver tissues from patients with non-alcoholic steatohepatitis (NASH), as well as in monosodium urate (MSU)-stimulated lymphatic endothelial cells (LECs) and influenza virus-infected human umbilical vein endothelial cells (HUVECs). R-loop regulatory proteins upregulated during metabolic inflammation were enriched in immune and inflammatory pathways. NRF2 was identified as a regulator of 27 R-loop regulatory proteins, including 10 positively and 17 negatively regulated proteins. Furthermore, 54 R-loop regulatory proteins overlapped with CRISPRi-identified mitochondrial and cellular ROS regulators, suggesting potential reciprocal regulation between R-loop homeostasis and ROS signaling. Disease-associated changes in pro-ROS and anti-ROS R-loop regulatory proteins further linked R-loop regulation to inflammatory and oxidative stress pathways. DISCUSSION: These findings identify reduced R-loop abundance at genomic regions encoding strongly upregulated inflammatory genes as a shared feature across multiple models of metabolic inflammation and influenza virus infection. The results further suggest that immune-associated R-loop regulatory proteins and the NRF2-ROS axis may contribute to R-loop remodeling during inflammatory disease. This integrative framework provides new insight into the potential role of R-loops and ROS-sensitive R-loop regulators in inflammatory and metabolic diseases and identifies candidate pathways for future mechanistic investigation and therapeutic targeting.

R-loop regulatory proteins↗
PubMed2025

Molecular mechanisms and breeding strategies for heat tolerance in vegetable crops under global warming.

Extreme heat driven by climate change poses a catastrophic threat to global vegetable production, undermining nutritional security because of the heightened physiological sensitivity and succulent tissues of these crops. This review synthesizes the multistage impacts of heat stress across critical developmental phases-from germination to reproduction-emphasizing morphological impairments (such as leaf wilting and floral abortion) and physiological disruptions (including photosynthetic inhibition and oxidative damage). We systematically dissect thermotolerance mechanisms in vegetables, highlighting transcriptional reprogramming by HSFs, WRKY, and NAC transcription factors; chaperone-mediated proteostasis via HSPs; epigenetic remodeling; Ca2+-ROS signaling pathways; and the role of phase separation dynamics. Importantly, we propose six strategic pathways to develop heat-resilient vegetables: harnessing natural variation through pan-genome-driven allele mining; employing biotechnological interventions such as CRISPR-mediated editing and synthetic promoters; engineering multistress tolerance by targeting conserved 'core response' pathways; exploiting epigenetic memory to achieve transgenerational resilience; optimizing source-sink dynamics with ''Climate-Responsive Carbon Optimization; and applying plant growth regulators and nanotechnology to enhance thermotolerance. Together, these strategies chart a clear roadmap for climate-smart vegetable breeding and call for interdisciplinary collaboration to translate molecular discoveries into practical breeding approaches for sustainable food systems under escalating thermal extremes.

Journal Article↗
PubMed2026

Allelochemical signaling and phytohormone crosstalk in plants: molecular mechanisms and implications for sustainable weed management.

Phytotoxic effects from allelopathy occur due to signaling pathways that induce alterations in hormonal balance within the plants, thereby hindering weed growth. Signaling crosstalk between various hormones and signaling pathways (Ca2⁺, MAPK, ROS) is involved in the molecular response mechanisms found through omics. Utilizing such mechanisms would help develop new environmentally friendly methods for sustainable weed management. Allelopathy serves as an essential component of plant-plant interaction via controlling the secretion of secondary metabolites (allelochemicals), which affect the growth, development, and physiological activity of nearby plants. The latest findings indicate that allelochemicals disturb phytohormone balance and signaling pathways resulting in oxidative stress, metabolism dysfunctions, cellular processes disturbances, and eventually inhibiting the growth of target weed species. Molecular biology progress and omics techniques brought information about the sophisticated regulation processes involved in allelopathic interactions. This review summarizes the information about the molecular mechanism of weed suppression mediated by allelopathy with the emphasis on allelochemical perception, phytohormone signaling, ROS responses, and evidence obtained by the application of transcriptomics, proteomics, metabolomics, and other omics-based studies. In addition, it introduces novel approaches, such as rhizosphere engineering, nanotechnologies, and genome editing, which may improve the effectiveness and reliability of allelopathic weed suppression. Overall, these achievements provide prospects for creating a new generation of weed control technologies that are sustainable, environmentally friendly, and climate-adaptive.

Plant Growth Regulators↗
PubMed2026

Translating Flood-Tolerance Biology into Breeding: A 5D Framework for Next-Generation Rice Varieties.

Flooding is among the most devastating abiotic stresses limiting rice productivity. Although SUB1A introgression conferred submergence tolerance in several mega-varieties, this single-gene approach is insufficient for the diverse flood types-flash floods, stagnant floods, anaerobic germination, and deepwater inundation-progressively intensifying with climate change. Here, we review the physiological mechanisms and genetic architecture underlying tolerance to each flood type, emphasizing the dual role of reactive oxygen species (ROS) in signalling and damage, the management of elemental toxicities (Fe2+, Mn2+) under altered soil redox, and lessons from wetland species and lowland rice. We then examine why marker-assisted selection has failed for polygenic, multi-stress tolerance and identify persistent breeding bottlenecks. Building on this biological foundation, we outline an integrated 5D framework (Demand, Discovery, Design, Development, Deployment) that links gene-bank diversity, multi-omics discovery, predictive breeding and on-farm validation through continuous feedback. We discuss how connected breeding, the transition-from-trait-to-environment (TTE) strategy, and speed breeding can accelerate genetic gain, and we close with research priorities centred on the biology of multi-flood tolerance to develop climate-resilient rice.

5D breeding framework↗
PubMed2024

IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways.

Senescent cells exert their effects through the release of various factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The SASP can induce senescence in healthy cells (secondary senescence), modulate immune system function, reshape the extracellular matrix, and facilitate cancer progression.Among SASP components, certain factors act as key regulators in the induction of secondary senescence. In this study, we evaluated the role of IGFBP7, a crucial SASP component. Our results demonstrated that ROS-prostaglandin signaling is involved in the release of IGFBP7. Furthermore, neutralizing antibodies targeting IGFBP7 attenuated the SASP's pro-senescence activity. Cells incubated with IGFBP7 also entered a state of senescence.The senescence induced by IGFBP7 appears to be mediated through three primary pathways. First, IGFBP7 can bind to insulin, thereby inhibiting its anti-senescence and pro-growth effects. In addition to this inhibitory effect on the insulin pathway, IGFBP7 may enhance IGFII pro-senescence signaling by promoting its interaction with IGF2R while blocking IGF1R. These activities are dependent on ERK and AKT signaling pathways. Finally, IGFBP7 and Activin A, both of which can induce cellular senescence, appear to regulate and inhibit each other, suggesting a compensatory mechanism to prevent excessive senescence. Notably, our preliminary data indicate that IGFBP7, in addition to blocking Activin A, may interact with its receptors and induce senescence via SMAD pathways.Our findings highlight that IGFBP7, along with other members of the IGFBP family, plays a pivotal role in senescence-related signaling pathways. Therefore, IGFBP7 may serve as a potential target for anti-aging strategies aimed at reducing the burden of senescence on tissues and organs.

Insulin-Like Growth Factor Binding Proteins↗
PubMed2026

RPLP0 drives diffuse large B-cell lymphoma cell proliferation through reactive oxygen species-dependent AKT/mTOR activation and inhibition of stress-induced autophagy.

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes. Identifying the primary molecular causes of DLBCL remains key. The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis. The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified. Hub genes were identified via protein-protein interaction network analysis. DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown. Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed. N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies. In the DLBCL datasets, six ribosome-associated genes were differentially expressed. RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G2-phase arrest, without impacting apoptosis. Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD+/NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization. Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles. Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited. NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression. These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.

AKT/mTOR signaling pathway↗
PubMed2026

Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species.

Reactive oxygen species (ROS) promote genomic instability and fuel oncogenic signaling in cancer, but antioxidant therapies have so far failed to improve, or worsen, cancer outcomes. Emerging data suggest that T cells depend on ROS for signal transduction. In this study, we show that tumors exploit this dependency, releasing antioxidant enzymes into the tumor environment to suppress T cell-mediated antitumor immunity. The interstitial fluid of tumors possesses potent antioxidant activity, associated with enrichment of the antioxidant enzyme peroxiredoxin 1 (PRDX1). Extracellular PRDX1 deprives T cells of ROS, preventing oxidative inactivation of phosphatases required for T cell receptor-driven kinase signaling and effector function. Prdx1 is up-regulated upon cancer immunoediting, and loss of PRDX1 within tumors enhances antitumor immunity and immunotherapy responses. These findings define a redox-dependent mechanism of tumor immunosuppression that is potentially amenable to therapeutic intervention.

Animals↗
PubMed2026

Oxidative stress and cancer: current insights and therapeutic implications.

OXIDATIVE STRESS: good or evil? Oxidative stress occurs when the balance between reactive oxygen species (ROS) and antioxidant defenses shifts toward an excess of ROS; while essential in physiological processes, it plays a context-dependent role in cancer, contributing to both the promotion and inhibition of tumorigenesis. Small to moderate amounts of ROS activate pathways supporting tumor progression and proliferation, while large amounts lead to genomic instability and cell death. ROS are generated endogenously and exogenously. In cancer, ROS activate pathways that prompt tumor development (KRAS, MYC, PI3K-Akt-mTOR) and block tumor suppressors (p53, BRCA1), allowing tumorigenesis and drug resistance. They also modulate the tumor microenvironment (TME) by altering tumor, stromal and immune cell interactions, which initiate angiogenesis, epithelial-mesenchymal transition (EMT), inflammation and metastasis. Myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) contribute to ROS-driven immunosuppression. Cancer cells mainly rely on glycolysis and oxidative phosphorylation (OXPHOS) to sustain their energetic and metabolic requirements. Generated ROS act as metabolic byproducts and signaling molecules supporting proliferation and tumorigenesis. Cancer stem cells (CSCs) produce low ROS levels by activating antioxidant pathways and mitochondria remodeling, ensuring recurrence and persistence. There is a redox duality that presents challenges and opportunities for therapies. Pro-oxidant approaches attempt to overwhelm the tumor's defenses, while antioxidants preserve healthy tissues. Advances in targeted redox modulation with immunotherapies improve therapy effectiveness. We propose a new "Adaptive Directed Redox Therapy" (ADRT), which involves a dynamic, feedback-controlled methodology that alternates pro- and antioxidant phases to selectively collapse tumor redox balance while preserving normal tissues.

Humans↗
PubMed2026

Angiotensin signaling is essential for stress erythropoiesis but causes retention of dysfunctional mitochondria in RBCs.

We previously reported that excessive angiotensin-II→AT receptor-1 (AT→ATR1) signaling results in sickle cell anemia-associated (SCA-associated) nephropathy. Herein, we showed that hyperangiotensinemia in SCA results from high erythroid cell-generated reactive oxygen species (ROS), which oxidized angiotensinogen (ATGN) and favored its rapid conversion to AT. Increased AT→ATR1 signaling in SCA erythroid cells generated ROS and created a positive feedback loop of ROS→oxidized ATGN→AT→ATR1→ROS, perpetuating the hyperangiotensinemia. ATR1 blocker, losartan, reduced erythrocyte ROS, oxidized ATGN, and AT levels. The ROS→AT→ATR1→ROS loop was driven by sickle erythropoiesis, as it was reproduced when WT mice were transplanted with SCA hematopoiesis. Using SCA and WT mice with germline- and erythroid-specific ATR1 deficiency, we found that stress erythropoiesis, but not steady-state erythropoiesis, was critically dependent on erythroid AT→ATR1 signaling, which acted in harmony with increased erythropoietin signaling. Furthermore, instead of the canonical AT→ATR1→NADPH-oxidase→ROS signaling in steady-state erythropoiesis, AT→ATR1 signaling in stress erythroid cells increased mitochondrial mass and dysfunctional mitochondria, which thereby increased ROS. SCA mice with erythroid-specific ATR1 deficiency had decreased RBC accumulation of dysfunctional mitochondria and decreased ROS, which reduced SCA-associated nephropathy. Overall, we demonstrate that AT→ATR1 signaling was essential for stress erythropoiesis but led to increased dysfunctional mitochondria retention in mature RBCs, which generated ROS and perpetuated hyperangiotensinemia, resulting in end-organ damage.

Animals↗
PubMed2016

The impact of metagenomic interplay on the mosquito redox homeostasis.

Mosquitoes are exposed to oxidative challenges throughout their life cycle. The primary challenge comes from a blood meal. The blood digestion turns the midgut into an oxidative environment, which imposes pressure not only on mosquito fecundity and other physiological traits but also on the microbiota in the midgut. During evolution, mosquitoes have developed numerous oxidative defense mechanisms to maintain redox homeostasis in the midgut. In addition to antioxidants, SOD, catalase, and glutathione system, sufficient supply of the reducing agent, NADPH, is vital for a successful defense against oxidative stress. Increasing evidence indicates that in response to oxidative stress, cells reconfigure metabolic pathways to increase the generation of NADPH through NADP-reducing networks including the pentose phosphate pathway and others. The microbial homeostasis is critical for the functional contributions to various host phenotypes. The symbiotic microbiota is regulated largely by the Duox-ROS pathway in Drosophila. In mosquitoes, Duox-ROS pathway, heme-mediated signaling, antimicrobial peptide production and C-type lectins work in concert to maintain the dynamic microbial community in the midgut. Microbial mechanisms against oxidative stress in this context are not well understood. Emerging evidence that microbial metabolites trigger host oxidative response warrants further study on the metagenomic interplay in an oxidative environment like mosquito gut ecosystem. Besides the classical Drosophila model, hematophagous insects like mosquitoes provide an alternative model system to study redox homeostasis in a symbiotic metagenomic context.

Animals↗
PubMed2026

Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs.

Recent developments in tuberculosis (TB) treatment have identified an enormous potential of host-directed therapies (HDT)) in achieving better and faster control of infection. We have previously demonstrated the synergistic effect of sertraline (SRT) with frontline TB drugs in clearing infection in murine tissues. Our attempts to uncover the mechanistic basis of this enhancement, using sertraline as a probe, help identify host signalling pathways critical for controlling Mycobacterium tuberculosis (Mtb). We identify a significant role for sertraline-mediated modulation of mitochondrial physiology and consequent reactive oxygen species (ROS) generation as a secondary signal, leading to greater IL-1β release and K+ efflux from macrophages via NLRP3 inflammasome activation. We thus highlight an important relationship between mitochondrial physiology and inflammasome activation, enabling infected macrophages to better control Mtb.

Animals↗
PubMed2025

Matrine alleviates coronary microvascular dysfunction in ischemia with non-obstructive coronary artery disease mice induced by advanced glycation end products inhibition of the reactive oxygen species-mediated endoplasmic reticulum stress in cardiac microvascular endothelial cells.

OBJECTIVE: To investigate the protective effect of matrine on coronary microvascular dysfunction (CMD) induced by advanced glycation end products (AGEs) in a mouse model of ischemia with non-obstructive coronary artery disease (INOCA), with a focus on the underlying mechanisms, particularly the endoplasmic reticulum (ER) stress protein kinase R-like ER kinase (PERK)/ nuclear factor of activated T-cells (NFAT) signaling pathway. METHODS: An INOCA model was established in mice, and CMD was induced by peritoneal injections of AGEs. Matrine was administered daily via intraperitoneal injections. Coronary microcirculation was evaluated using coronary flow velocity reserve (CFVR), and cardiac microvascular endothelial cells (CMECs) were isolated for assessment of apoptosis, inflammation, oxidative stress, and microthrombosis. Markers of ER stress and the PERK/NFAT pathway were examined through immunoblotting, immunofluorescence, and enzymatic assays. The effect of matrine were further evaluated in CMECs treated with AGEs and the PERK agonist. RESULTS: Matrine treatment significantly improved CFVR and reduced CMD in AGEs-exposed INOCA mice. In CMECs, matrine attenuated AGEs-induced apoptosis, inflammation, and microthrombosis. It also suppressed intracellular reactive oxygen species (ROS) generation, ER stress markers, and PERK/NFAT signaling. Matrine's effects were concentration-dependent and partially reversed by the PERK agonist, confirming its action through the ER stress pathway. No significant toxicities were observed with matrine administration. CONCLUSION: Matrine attenuates AGEs-induced CMD in INOCA by suppressing the ROS-mediated ER stress PERK/NFAT signaling pathway in CMECs. This study highlights matrine's potential as a therapeutic agent for CMD in diabetic cardiovascular complications.

Animals↗
PubMed2026

Oxeiptosis - potential in cancer treatment?

Oxeiptosis is a reactive oxygen species (ROS)-dependent form of programmed cell death that plays a key role in cellular homeostasis and holds promise as a cancer therapy. This review explores its molecular mechanisms, emphasizing the KEAP1-PGAM5-AIFM1 signalling pathway and its reliance on ROS accumulation. Compared to other cell death pathways, oxeiptosis offers a distinct approach, especially for targeting cancer cells resistant to conventional therapies. The review evaluates emerging inducers, both synthetic and natural, that selectively trigger oxeiptosis in cancer cells. It also examines the potential synergy between oxeiptosis and ROS-generating chemotherapies, particularly in the oxidative tumour microenvironment. However, challenges remain, including identifying tumour-specific inducers, overcoming cancer cell resistance to oxidative stress and reducing off-target effects. The review concludes by highlighting the need for targeted delivery strategies and rigorous preclinical studies to translate oxeiptosis into effective cancer treatments. Overall, it underscores oxeiptosis as a promising avenue to address drug resistance and improve therapeutic outcomes in oncology.

Humans↗
PubMed2026

Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits.

SIGNIFICANCE: Nicotine from tobacco products, secondhand smoke, and emerging delivery systems remains a major but underappreciated driver of gastric carcinogenesis (GC). Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs via spatially compartmentalized NOX signaling. RECENT ADVANCES: We synthesize evidence for a unified model wherein nicotine activates nAChR/β-AR signaling, Ca2+ influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX/ROS/NF-κB/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT/metastasis (ABL1/STAT3/COX-2/periostin), survival/chemoresistance (ERK/GLI1/Bcl-2), and invasion/immune evasion (miR-21/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior. CRITICAL ISSUES: A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from in vitro studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored. FUTURE DIRECTIONS: We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy. Antioxid. Redox Signal. 00, 000-000.

gastric cancer↗
PubMed2026

CD4+T cell metabolic reprogramming as therapeutic targets in neurodegenerative diseases.

Neurodegenerative diseases are a group of disorders characterized by the progressive loss of structure and function of neurons in the brain and/or peripheral nervous system. The main pathological feature of neurodegenerative disease in the central nervous system (CNS) is the selective neuronal loss in the brain and spinal cord, leading to cognitive and/or motor dysfunction. The immune system plays a variety of roles in the pathophysiology of neurodegenerative diseases. CD4+T cells are being recognized as important immunometabolic modulators in the pathophysiology of neurodegenerative disorders (ND), including multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). Their varied metabolic patterns provide a special therapeutic window for regulating neuroinflammation, spanning from lipid-dependent regulatory T cells (Tregs) to glycolysis-driven pro-inflammatory subsets (Th1, Th17). Abnormal immune metabolism raises the risk of oxidative stress, mitochondrial malfunction, and neuronal death in neurodegenerative environments. According to recent research, altering CD4 T cell metabolism to favour oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) may help Treg function return and inhibit harmful effector responses. Current research on CD4 T cell immunometabolic pathways, their interactions with CNS-resident cells, and the developing possibility of metabolic intervention to slow neurodegeneration is explained in this review. By examining important signaling pathways including AMPK, mTORC1, and ROS dynamics, we demonstrate how CD4+T cell metabolism may reshape ND treatment approaches.

Humans↗
PubMed2026

Abscisic acid promotes RBOH-dependent reactive oxygen species production and lignin biosynthesis in pears via the PuABI5-PuMYB169 module.

Pear stone cell lignification, a critical determinant of fruit texture and quality, is regulated by developmental and environmental cues, with abscisic acid (ABA) playing a central role. However, the molecular mechanisms underlying its role in reactive oxygen species (ROS)-mediated lignification remain unclear. Here, we show that PuABI5, a key component in ABA signaling, directly combines with PuMYB169, the master regulator of stone cell lignification, to modulate ROS production and lignin biosynthesis in pear fruit. Exogenous application of ABA enhances H2O2 and lignin accumulation in both pear fruits and calli, and ABA-activated PuABI5 positively regulates stone cell lignification. We demonstrate that ABA-induced PuABI5 binds directly to the PuMYB169 promoter and activates its expression to promote the transcription of PuRBOHF and lignin-related genes, thereby enhancing ROS production and lignin accumulation. Notably, PuABI5 interacted with PuMYB169 to enhance the induction of PuRBOHF expression, leading to elevated levels of H2O2, which feedback to strengthen the interaction between PuABI5 and PuMYB169. Collectively, our findings elucidate that ABA induces ROS-mediated lignification of stone cells in pears by activating the PuABI5-PuMYB169 transcriptional module.

Lignin↗