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Search Results (1,525)

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Keywords = stress response molecules

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18 pages, 1602 KiB  
Article
Interacting Effects of Heat and Nanoplastics Affect Wheat (Triticum turgidum L.) Seedling Growth and Physiology
by Debora Fontanini, Stefania Bottega, Monica Ruffini Castiglione and Carmelina Spanò
Plants 2025, 14(15), 2426; https://doi.org/10.3390/plants14152426 - 5 Aug 2025
Abstract
Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that [...] Read more.
Nano- and microplastic pollution, together with the ongoing rise in global temperatures driven by climate change, represent increasingly critical environmental challenges. Although these stressors often co-occur in the environment, their combined effects on plant systems remain largely unexplored. To test the hypothesis that their interaction may exacerbate the effects observed under each stressor individually, we investigated the response of seedlings of Triticum turgidum to treatments with fluorescent polystyrene nanoplastics under optimal (25 °C) and elevated (35 °C) temperature conditions. We evaluated seedling growth, photosynthetic pigment content, and oxidative stress markers using both biochemical and histochemical techniques. In addition, we assessed enzymatic and non-enzymatic antioxidant responses. The use of fluorescently labeled nanoplastics enabled the visualization of their uptake and translocation within plant tissues. Elevated temperatures negatively affect plant growth, increasing the production of proline, a key protective molecule, and weakly activating secondary defense mechanisms. Nanoplastics disturbed wheat seedling physiology, with these effects being amplified under high temperature conditions. Combined stress enhances nanoplastic uptake in roots, increases oxidative damage, and alters antioxidant responses, reducing defense capacity in leaves while triggering compensatory mechanisms in roots. These findings underscore a concerning interaction between plastic pollution and climate warming in crop plants. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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17 pages, 7024 KiB  
Article
Proteomic Analysis of Differentially Expressed Plasma Exosome Proteins in Heat-Stressed Holstein cows
by Shuwen Xia, Yingying Jiang, Wenjie Li, Zhenjiang An, Yangyang Shen, Qiang Ding and Kunlin Chen
Animals 2025, 15(15), 2286; https://doi.org/10.3390/ani15152286 - 5 Aug 2025
Abstract
Heat stress in dairy cows, caused by high temperature and humidity during summer, has led to significant declines in milk production and severe economic losses for farms. Exosomes—extracellular vesicles carrying bioactive molecules—are critical for intercellular communication and immunity but remain understudied in heat-stressed [...] Read more.
Heat stress in dairy cows, caused by high temperature and humidity during summer, has led to significant declines in milk production and severe economic losses for farms. Exosomes—extracellular vesicles carrying bioactive molecules—are critical for intercellular communication and immunity but remain understudied in heat-stressed Holstein cows. In this study, we extracted exosomes from three heat-stressed (HS) cows and three non-heat-stressed (Ctr) cows and employed proteomics to analyze plasma exosomes. We identified a total of 28 upregulated and 18 downregulated proteins in the HS group compared to the control group. Notably, we observed a significant upregulation of key protein groups, including cytoskeletal regulators, signaling mediators, and coagulation factors, alongside the downregulation of HP-25_1. These differentially expressed proteins demonstrate strong potential as heat stress biomarkers. GO and KEGG analyses linked the differentially expressed proteins to actin cytoskeleton regulation and endoplasmic reticulum pathways. Additionally, protein–protein interaction (PPI) analysis revealed the PI3K-Akt signaling pathway as a central node in the cellular response to heat stress. These findings establish plasma exosomes as valuable biospecimens, provide valuable insights into the molecular mechanisms of heat stress response, and may contribute to the development of precision breeding strategies for enhanced thermal resilience in dairy herds. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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42 pages, 1407 KiB  
Review
Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes
by Charles F. Manful, Eric Fordjour, Dasinaa Subramaniam, Albert A. Sey, Lord Abbey and Raymond Thomas
Int. J. Mol. Sci. 2025, 26(15), 7520; https://doi.org/10.3390/ijms26157520 (registering DOI) - 4 Aug 2025
Abstract
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. [...] Read more.
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases. Full article
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16 pages, 19172 KiB  
Communication
DEAD-Box Helicase 3 Modulates the Non-Coding RNA Pool in Ribonucleoprotein Condensates During Stress Granule Formation
by Elizaveta Korunova, B. Celia Cui, Hao Ji, Aliaksandra Sikirzhytskaya, Srestha Samaddar, Mengqian Chen, Vitali Sikirzhytski and Michael Shtutman
Non-Coding RNA 2025, 11(4), 59; https://doi.org/10.3390/ncrna11040059 - 1 Aug 2025
Viewed by 156
Abstract
Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of [...] Read more.
Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of mammalian stress granules is the DEAD-box RNA helicase DDX3, which unwinds RNA in an ATP-dependent manner. DDX3 is involved in multiple steps of RNA metabolism, facilitating gene transcription, splicing, and nuclear export and regulating cytoplasmic translation. In this study, we investigate the role of the RNA helicase DDX3’s enzymatic activity in shaping the RNA content of ribonucleoprotein (RNP) condensates formed during arsenite-induced stress by inhibiting DDX3 activity with RK-33, a small molecule previously shown to be effective in cancer clinical studies. Using the human osteosarcoma U2OS cell line, we purified the RNP granule fraction and performed RNA sequencing to assess changes in the RNA pool. Our results reveal that RK-33 treatment alters the composition of non-coding RNAs within the RNP granule fraction. We observed a DDX3-dependent increase in circular RNA (circRNA) content and alterations in the granule-associated intronic RNAs, suggesting a novel role for DDX3 in regulating the cytoplasmic redistribution of non-coding RNAs. Full article
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14 pages, 1769 KiB  
Article
The Effect of Colors and Light Intensity on the Growth and Biochemical Compounds of the Chlorophyceae Nephroselmis sp.
by Ichrak Sekri, Wassim Guermazi, Mohamad El-khateeb, George N. Hotos and Habib Ayadi
J. Mar. Sci. Eng. 2025, 13(8), 1452; https://doi.org/10.3390/jmse13081452 - 29 Jul 2025
Viewed by 262
Abstract
Light intensity and spectral quality play crucial roles in microalgal growth and biochemical biosynthesis. This study investigates the effects of different light intensities (3000, 8000 and 15,000 lux) and colors (red, white, yellow and green) on the growth and metabolites of Nephroselmis sp. [...] Read more.
Light intensity and spectral quality play crucial roles in microalgal growth and biochemical biosynthesis. This study investigates the effects of different light intensities (3000, 8000 and 15,000 lux) and colors (red, white, yellow and green) on the growth and metabolites of Nephroselmis sp. Moderate intensity (8000 lux) of white light is sufficient to produce this microalga. The colors of light strongly affect the parameters of the growth of Nephroselmis under each light intensity (p < 0.05). The yellow and green light supported the highest growth rates for the three intensities. Blue and green light at 15,000 Lux stimulates high levels of chl-a corresponding to antenna size 2.80 and 2.46. Nephroselmis illuminated with red light synthesizes carotenoids reaching 13 µg mL−1 at 15,000 lux. This latter for each color stops the proliferation of Nephroselmis, and cells shift their metabolism towards the accumulation of protein. Nephroselmis accumulates more protein, followed by carbohydrates, lipids and polyphenols. Nephroselmis exhibited the highest protein (64% D.W) content when cultured under white light, and the green at 15,000 lux enhanced their production. Nephroselmis is rich in carbohydrates, which accounted for more than 20% D.W under all combinations of light intensities and colors. The accumulation of polyphenols and carotenoids under high-intensity red and white light may reflect an oxidative stress response, suggesting their role as protective antioxidants. The capacity of Nephroselmis sp. to thrive and synthesize valuable metabolites under variable light regimes underscores its potential as a robust candidate for the production of various molecules. Full article
(This article belongs to the Section Marine Aquaculture)
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36 pages, 5612 KiB  
Review
The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs
by Bolong Xu, Ayitila Maimaitijiang, Dawuti Nuerbiyamu, Zhengding Su and Wenfang Li
Biomolecules 2025, 15(8), 1088; https://doi.org/10.3390/biom15081088 - 27 Jul 2025
Viewed by 488
Abstract
The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and [...] Read more.
The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and resistance to treatment. Exploring the diverse roles of p53, which include regulating the cell cycle, repairing DNA, inducing apoptosis, reprogramming metabolism, and modulating immunity, provides valuable insights into cancer mechanisms and potential treatments. This review integrates recent findings on p53′s dual nature, functioning as both a tumor suppressor and an oncogenic promoter, depending on the context. Wild-type p53 suppresses tumors by inducing cell cycle arrest or apoptosis in response to genotoxic stress, while mutated variants often lose these functions or gain novel pro-oncogenic activities. Emerging evidence highlights p53′s involvement in non-canonical pathways, such as regulating tumor microenvironment interactions, metabolic flexibility, and immune evasion mechanisms. For instance, p53 modulates immune checkpoint expression and influences the efficacy of immunotherapies, including PD-1/PD-L1 blockade. Furthermore, advancements in precision diagnostics, such as liquid biopsy-based detection of p53 mutations and AI-driven bioinformatics tools, enable early cancer identification and stratification of patients likely to benefit from targeted therapies. Therapeutic strategies targeting p53 pathways are rapidly evolving. Small molecules restoring wild-type p53 activity or disrupting mutant p53 interactions, such as APR-246 and MDM2 inhibitors, show promise in clinical trials. Combination approaches integrating gene editing with synthetic lethal strategies aim to exploit p53-dependent vulnerabilities. Additionally, leveraging p53′s immunomodulatory effects through vaccine development or adjuvants may enhance immunotherapy responses. In conclusion, deciphering p53′s complex biology underscores its unparalleled potential as a biomarker and therapeutic target. Integrating multi-omics analyses, functional genomic screens, and real-world clinical data will accelerate the translation of p53-focused research into precision oncology breakthroughs, ultimately improving patient outcomes. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Cancer Treatment)
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18 pages, 5168 KiB  
Article
Arabidopsis Antiporter Genes as Targets of NO Signalling: Phylogenetic, Structural, and Expression Analysis
by Rabia Amir, Zuhra Qayyum, Sajeel Hussain, Byung-Wook Yun, Adil Hussain and Bong-Gyu Mun
Int. J. Mol. Sci. 2025, 26(15), 7195; https://doi.org/10.3390/ijms26157195 - 25 Jul 2025
Viewed by 179
Abstract
Nitric oxide is a gaseous signalling molecule produced by plants. Slight changes in endogenous NO levels have significant biochemical and physiological consequences. We investigated the structural and functional properties of NO-responsive antiporter genes in Arabidopsis thaliana. Phylogenetic analysis of 50 antiporter genes [...] Read more.
Nitric oxide is a gaseous signalling molecule produced by plants. Slight changes in endogenous NO levels have significant biochemical and physiological consequences. We investigated the structural and functional properties of NO-responsive antiporter genes in Arabidopsis thaliana. Phylogenetic analysis of 50 antiporter genes classified them into four subgroups based on the presence of NHX and CPA domains and the evolutionary similarity of the protein sequences. Antiporters were found scattered across the five chromosomes with unique physico-chemical properties and subcellular localisation in the plasma membrane, nucleus, chloroplasts, and vacuole. Furthermore, we performed QPCR analysis of eight different antiporter genes after infiltrating the plants with 1 mM CySNO (S-nitroso-L-cysteine), a nitric oxide donor, in WT and the loss-of-function atgsnor1-3 (disruptive S-nitrosoglutathione reductase 1 activity) plants. The AT1G79400 (CHX2), AT2G38170 (RCI4), and AT5G17400 (ER-ANT1) showed a significant increase in their expression in response to CySNO infiltration. However, their expression in atgsnor1-3 plants was found to be lower than in the WT plants, indicating a significant redundancy in the response of these genes to 1 mM levels of CySNO and physiological levels of SNOs in atgsnor1-3. On the other hand, a significant reduction in the expression of AT1G16380 (CHX1), AT2G47600 (MHX1), AT3G13320 (CAX2), and AT5G11800 (KEA6) was observed in WT plants after CySNO infiltration as well as in the leaves of atgsnor1-3 plants. Our study identified three NO-responsive antiporter genes in Arabidopsis, indicating their roles in stress responsiveness and ion homeostasis that could be used for further validation of their roles in NO signalling in plants. Full article
(This article belongs to the Special Issue Nitric Oxide Signalling in Plants)
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27 pages, 2494 KiB  
Review
Redox-Epigenetic Crosstalk in Plant Stress Responses: The Roles of Reactive Oxygen and Nitrogen Species in Modulating Chromatin Dynamics
by Cengiz Kaya and Ioannis-Dimosthenis S. Adamakis
Int. J. Mol. Sci. 2025, 26(15), 7167; https://doi.org/10.3390/ijms26157167 - 24 Jul 2025
Viewed by 412
Abstract
Plants are constantly exposed to environmental stressors such as drought, salinity, and extreme temperatures, which threaten their growth and productivity. To counter these challenges, they employ complex molecular defense systems, including epigenetic modifications that regulate gene expression without altering the underlying DNA sequence. [...] Read more.
Plants are constantly exposed to environmental stressors such as drought, salinity, and extreme temperatures, which threaten their growth and productivity. To counter these challenges, they employ complex molecular defense systems, including epigenetic modifications that regulate gene expression without altering the underlying DNA sequence. This review comprehensively examines the emerging roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as central signaling molecules orchestrating epigenetic changes in response to abiotic stress. In addition, biotic factors such as pathogen infection and microbial interactions are considered for their ability to trigger ROS/RNS generation and epigenetic remodeling. It explores how ROS and RNS influence DNA methylation, histone modifications, and small RNA pathways, thereby modulating chromatin structure and stress-responsive gene expression. Mechanistic insights into redox-mediated regulation of DNA methyltransferases, histone acetyltransferases, and microRNA expression are discussed in the context of plant stress resilience. The review also highlights cutting-edge epigenomic technologies such as whole-genome bisulfite sequencing (WGBS), chromatin immunoprecipitation sequencing (ChIP-seq), and small RNA sequencing, which are enabling precise mapping of stress-induced epigenetic landscapes. By integrating redox biology with epigenetics, this work provides a novel framework for engineering climate-resilient crops through the targeted manipulation of stress-responsive epigenomic signatures. Full article
(This article belongs to the Section Molecular Biology)
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20 pages, 4054 KiB  
Article
Identification of Auxin-Associated Genes in Wheat Through Comparative Transcriptome Analysis and Validation of the Candidate Receptor-like Kinase Gene TaPBL7-2B in Arabidopsis
by Mengjie Zhang, Guangzhu Chen, Jie Cai, Yongjie Ji, Linrun Xiang, Xinhong Chen and Jun Wang
Plants 2025, 14(15), 2277; https://doi.org/10.3390/plants14152277 - 24 Jul 2025
Viewed by 279
Abstract
Auxin (IAA), a key natural signaling molecule, plays a pivotal role in regulating plant growth, development, and stress responses. Understanding its signal transduction mechanisms is crucial for improving crop yields. In this study, we conducted a comparative transcriptome analysis of wheat leaf and [...] Read more.
Auxin (IAA), a key natural signaling molecule, plays a pivotal role in regulating plant growth, development, and stress responses. Understanding its signal transduction mechanisms is crucial for improving crop yields. In this study, we conducted a comparative transcriptome analysis of wheat leaf and root tissues treated with different concentrations of IAA (0, 1, and 50 μM). Functional enrichment analysis revealed that differentially expressed genes (DEGs) exhibited tissue-specific regulatory patterns in response to auxin. Weighted Gene Co-expression Network Analysis (WGCNA) identified receptor-like kinase genes within the MEgreen module as highly correlated with auxin response, suggesting their involvement in both root and leaf regulation. Among them, TaPBL7-2B, a receptor-like kinase gene significantly upregulated under 50 μM IAA treatment, was selected for functional validation. Ectopic overexpression of TaPBL7-2B in Arabidopsis thaliana (Col-0) enhanced auxin sensitivity and inhibited plant growth by suppressing root development and leaf expansion. In contrast, knockout of the Arabidopsis homolog AtPBL7 reduced auxin sensitivity and promoted both root and leaf growth. Transcriptome analysis of Col-0, the TaPBL7-2B overexpression line, and the pbl7 mutant indicated that TaPBL7-2B primarily functions through the MAPK signaling pathway and plant hormone signal transduction pathway. Furthermore, qRT-PCR analysis of wheat varieties with differing auxin sensitivities confirmed a positive correlation between TaPBL7-2B expression and auxin response. In conclusion, TaPBL7-2B acts as a negative regulator of plant growth, affecting root development and leaf expansion in both Arabidopsis and wheat. These findings enhance our understanding of auxin signaling and provide new insights for optimizing crop architecture and productivity. Full article
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16 pages, 1068 KiB  
Article
Protective Effects of Regular Physical Activity: Differential Expression of FGF21, GDF15, and Their Receptors in Trained and Untrained Individuals
by Paulina Małkowska, Patrycja Tomasiak, Marta Tkacz, Katarzyna Zgutka, Maciej Tarnowski, Agnieszka Maciejewska-Skrendo, Rafał Buryta, Łukasz Rosiński and Marek Sawczuk
Int. J. Mol. Sci. 2025, 26(15), 7115; https://doi.org/10.3390/ijms26157115 - 23 Jul 2025
Viewed by 188
Abstract
According to the World Health Organization (WHO), a healthy lifestyle is defined as a way of living that lowers the risk of becoming seriously ill or dying prematurely. Physical activity, as a well-known contributor to overall health, plays a vital role in supporting [...] Read more.
According to the World Health Organization (WHO), a healthy lifestyle is defined as a way of living that lowers the risk of becoming seriously ill or dying prematurely. Physical activity, as a well-known contributor to overall health, plays a vital role in supporting such a lifestyle. Exercise induces complex molecular responses that mediate both acute metabolic stress and long-term physiological adaptations. FGF21 (fibroblast growth factor 21) and GDF15 (growth differentiation factor 15) are recognized as metabolic stress markers, while their receptors play critical roles in cellular signaling. However, the differential gene expression patterns of these molecules in trained and untrained individuals following exhaustive exercise remain poorly understood. This study aimed to examine the transcriptional and protein-level responses in trained and untrained individuals performed a treadmill maximal exercise test to voluntary exhaustion. Blood samples were collected at six time points (pre-exercise, immediately post-exercise, and 0.5 h, 6 h, 24 h, and 48 h post-exercise). Gene expression of FGF21, GDF15, FGFR1 (fibroblast growth factor receptors), FGFR3, FGFR4, KLB (β-klotho), and GFRAL (glial cell line-derived neurotrophic factor receptor alpha-like) was analyzed using RT-qPCR, while plasma protein levels of FGF21 and GDF15 were quantified via ELISA. The results obtained were statistically analyzed by using Shapiro–Wilk, Mann–Whitney U, and Wilcoxon tests in Statistica 13 software. Untrained individuals demonstrated significant post-exercise upregulation of FGFR3, FGFR4, KLB, and GFRAL. FGF21 and GDF15 protein levels were consistently lower in trained individuals (p < 0.01), with no significant correlations between gene and protein expression. Trained individuals showed more stable expression of genes, while untrained individuals exhibited transient upregulation of genes after exercise. Full article
(This article belongs to the Special Issue Cytokines in Inflammation and Health)
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16 pages, 11002 KiB  
Article
Transcriptomic Identification of Key Genes Responding to High Heat Stress in Moso Bamboo (Phyllostachys edulis)
by Qinchao Fu, Xinlan Wen, Man Tang, Xin Zhao and Fang Liu
Genes 2025, 16(8), 855; https://doi.org/10.3390/genes16080855 - 23 Jul 2025
Viewed by 263
Abstract
Background/Objectives: Moso bamboo (Phyllostachys edulis), the most widely distributed bamboo species in China, is valued for both its shoots and timber. This species often faces challenges from high-temperature stress. To cope with this stress, Moso bamboo has evolved various adaptive mechanisms [...] Read more.
Background/Objectives: Moso bamboo (Phyllostachys edulis), the most widely distributed bamboo species in China, is valued for both its shoots and timber. This species often faces challenges from high-temperature stress. To cope with this stress, Moso bamboo has evolved various adaptive mechanisms at the physiological and molecular levels. Although numerous studies have revealed that a large number of transcription factors (TFs) and genes play important roles in the regulatory network of plant heat stress responses, the regulatory network involved in heat responses remains incompletely understood. Methods: In this study, Moso bamboo was placed in a high-temperature environment of 42 °C for 1 h and 24 h, and transcriptome sequencing was carried out to accurately identify key molecules affected by high temperature and their related biological pathways. Results: Through a differential expression analysis, we successfully identified a series of key candidate genes and transcription factors involved in heat stress responses, including members of the ethylene response factor, HSF, WRKY, MYB, and bHLH families. Notably, in addition to traditional heat shock proteins/factors, multiple genes related to lipid metabolism, antioxidant enzymes, dehydration responses, and hormone signal transduction were found to play significant roles in heat stress responses. To further verify the changes in the expression of these genes, we used qRT-PCR technology for detection, and the results strongly supported their key roles in cellular physiological processes and heat stress responses. Conclusions: This study not only deepens our understanding of plant strategies for coping with and defending against extreme abiotic stresses but also provides valuable insights for future research on heat tolerance in Moso bamboo and other plants. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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17 pages, 1361 KiB  
Review
Molecular Foundations of Neuroplasticity in Brain Tumours: From Microscopic Adaptation to Functional Reorganisation
by Lizeth Vinueza, Salvador Pineda and Jose E. Leon-Rojas
Int. J. Mol. Sci. 2025, 26(15), 7049; https://doi.org/10.3390/ijms26157049 - 22 Jul 2025
Viewed by 268
Abstract
Brain tumours challenge the structural and functional integrity of the brain, yet remarkable neuroplastic adaptations often preserve critical functions. This review synthesises the current knowledge of the molecular events underlying neuroplasticity in the context of tumoural growth, spanning from early genetic and protein [...] Read more.
Brain tumours challenge the structural and functional integrity of the brain, yet remarkable neuroplastic adaptations often preserve critical functions. This review synthesises the current knowledge of the molecular events underlying neuroplasticity in the context of tumoural growth, spanning from early genetic and protein alterations to macroscopic functional reorganisation. We discuss the roles of stress-regulated molecules, synaptic proteins, trophic factors, and morphological changes in driving adaptive responses. Furthermore, we bridge the gap between microscopic molecular events and large-scale network adaptations, emphasising clinical implications for glioma surgery and patient outcomes. Despite advances, knowledge gaps persist regarding the dynamics, predictors, and therapeutic modulation of plasticity, underscoring the need for future longitudinal and translational research. Understanding and leveraging these molecular mechanisms holds promise for improving functional recovery and quality of life in patients with brain tumours. Full article
(This article belongs to the Special Issue Brain Plasticity in Health and Disease)
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22 pages, 1008 KiB  
Review
Ap4A in Cancer: A Multifaceted Regulator and Emerging Therapeutic Target
by Kateryna Tkachenko, Tiziana Bachetti and Camillo Rosano
Molecules 2025, 30(15), 3056; https://doi.org/10.3390/molecules30153056 - 22 Jul 2025
Viewed by 325
Abstract
Diadenosine polyphosphates, including diadenosine tetraphosphate (Ap4A), are ubiquitous nucleotides that are present across diverse life forms, gaining considerable interest due to their role as cellular signaling molecules. Ap4A, in particular, has been extensively researched in various biological systems, especially under conditions of environmental [...] Read more.
Diadenosine polyphosphates, including diadenosine tetraphosphate (Ap4A), are ubiquitous nucleotides that are present across diverse life forms, gaining considerable interest due to their role as cellular signaling molecules. Ap4A, in particular, has been extensively researched in various biological systems, especially under conditions of environmental stress. This review provides an in-depth analysis of the current knowledge surrounding Ap4A, focusing on its biosynthesis and degradation pathways, the identification of Ap4A protein targets and the molecular mechanisms underlying its action. Furthermore, this review aims to examine the interplay between the various pathogenetic mechanisms driving tumor development and the potential role of Ap4A which emerges as pivotal signaling molecules orchestrating cellular responses to environmental challenges, positioning them at the nexus of cancer adaptation and progression. Full article
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24 pages, 1438 KiB  
Article
Neonatal Handling Positively Modulates Anxiety, Sensorimotor Gating, Working Memory, and Cortico-Hippocampal Neuroplastic Adaptations in Two Genetically Selected Rat Strains Differing in Emotional and Cognitive Traits
by Cristóbal Río-Álamos, Maria P. Serra, Francesco Sanna, Maria A. Piludu, Marianna Boi, Toni Cañete, Daniel Sampedro-Viana, Ignasi Oliveras, Adolf Tobeña, Maria G. Corda, Osvaldo Giorgi, Alberto Fernández-Teruel and Marina Quartu
Brain Sci. 2025, 15(8), 776; https://doi.org/10.3390/brainsci15080776 - 22 Jul 2025
Viewed by 355
Abstract
Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene [...] Read more.
Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article
(This article belongs to the Section Behavioral Neuroscience)
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25 pages, 2667 KiB  
Review
Nitric Oxide and Photosynthesis Interplay in Plant Interactions with Pathogens
by Elżbieta Kuźniak and Iwona Ciereszko
Int. J. Mol. Sci. 2025, 26(14), 6964; https://doi.org/10.3390/ijms26146964 - 20 Jul 2025
Viewed by 354
Abstract
Nitric oxide and reactive nitrogen species are key signalling molecules with pleiotropic effects in plants. They are crucial elements of the redox regulation of plant stress responses to abiotic and biotic stresses. Nitric oxide is known to enhance photosynthetic efficiency under abiotic stress, [...] Read more.
Nitric oxide and reactive nitrogen species are key signalling molecules with pleiotropic effects in plants. They are crucial elements of the redox regulation of plant stress responses to abiotic and biotic stresses. Nitric oxide is known to enhance photosynthetic efficiency under abiotic stress, and reactive nitrogen species-mediated alterations in photosynthetic metabolism have been shown to confer resistance to abiotic stresses. However, knowledge about the role of reactive nitrogen species in plant immune responses remains limited. In this review, we highlight recent advancements in understanding the role of NO in regulating stomatal movement, which contributes to resistance against pathogens. We will examine the involvement of NO in the regulation of photosynthesis, which provides energy, reducing equivalents and carbon skeletons for defence, as well as the significance of protein S-nitrosylation in relation to immune responses. The role of NO synthesis induced in pathogenic organisms during plant–pathogen interactions, along with S-nitrosylation of pathogen effectors to counteract their pathogenesis-promoting activity, is also reported. We will discuss the progress in understanding the interactions between reactive nitrogen species and photosynthetic metabolism, focusing on enhancing crop plants’ productivity and resistance in challenging environmental conditions. Full article
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