Jinghui Wang, Lupeng Gou, Haohai You, Feng Wang, Jie Zhu, Yinqi Wang, Zijian Xia, Zhuoduojie Kuan, Zhaohui Wang
{"title":"Untargeted Metabolomics Reveals Regional and Cultivar-Associated Metabolomic Variation in Soybeans Across Northeast China.","authors":"Jinghui Wang, Lupeng Gou, Haohai You, Feng Wang, Jie Zhu, Yinqi Wang, Zijian Xia, Zhuoduojie Kuan, Zhaohui Wang","doi":"10.3390/ijms27198925","DOIUrl":"10.3390/ijms27198925","url":null,"abstract":"<p><p>Soybean (Glycine max) quality and metabolic composition are shaped by complex interactions between genetic background and agro-ecological conditions, making metabolic characterization across major production regions valuable for germplasm evaluation and quality-oriented breeding. In this study, an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach was applied to compare the mature seed metabolomes of nine representative commercial soybean cultivars sampled from two major production regions in Northeast China: Heilongjiang (HLJ, four cultivars from Harbin) and Liaoning (LN, five cultivars from Shenyang). Because region-specific cultivars were collected from a single site and seed lot per province without direct site-level meteorological or soil measurements, genotype and environment are confounded in this observational design, and the observed differences reflect the combined variation in the sampled cultivar-location cohorts. After preprocessing, 8283 features were putatively annotated (MSI Level 2/3). Multivariate statistical analyses (PCA, PLS-DA, and OPLS-DA) combined with cultivar-grouped cross-validation revealed clear metabolic separation between the sampled HLJ and LN cohorts. A total of 1485 putatively annotated metabolites (VIP > 1.0, subsample-level FDR < 0.05, fold change HLJ/LN > 2.0 or <0.5) were screened as exploratory candidate differential metabolites, with 953 exhibiting higher abundance (FC>2.0) and 532 exhibiting lower abundance (FC<0.5, i.e., higher abundance in LN) in HLJ soybeans relative to LN soybeans. Exploratory KEGG pathway mapping (based on nominal p-values, as no pathway reached FDR-adjusted q<0.05) indicated nominal enrichment in isoflavonoid biosynthesis (p=0.0043, q=0.261) and tryptophan metabolism (p=0.0093, q=0.283); specifically, sampled LN cultivar-location combinations exhibited higher steady-state abundances of isoflavones and their glycosylated derivatives, whereas sampled HLJ soybeans exhibited higher steady-state abundances of specific lipid species (unsaturated fatty acyls, sphingolipids) and tryptophan-derived indoleamines. In the absence of direct environmental measurements, potential links between these steady-state metabolic signatures and regional macroclimatic differences (such as thermal regimes or high-latitude cold stress) are proposed strictly as exploratory, literature-informed hypotheses. Overall, these findings provide preliminary candidate metabolic markers for characterizing the sampled regional soybean germplasm; however, independent validation across additional harvest years, multiple geographic sites, independent seed lots, and broader cultivar panels will be required before these candidate metabolites can be considered validated biomarkers for geographic authentication.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Max L Silverstein, Sophia Hou, Chunxi Ge, Tanya C Garcia, Charles K F Chan, Karl C Bruckman, Eri Takematsu
{"title":"Bone Morphogenetic Protein-2 and Cabozantinib for Temporomandibular Joint Cartilage Repair: Murine and Porcine Injury Models.","authors":"Max L Silverstein, Sophia Hou, Chunxi Ge, Tanya C Garcia, Charles K F Chan, Karl C Bruckman, Eri Takematsu","doi":"10.3390/ijms27198937","DOIUrl":"10.3390/ijms27198937","url":null,"abstract":"<p><p>Temporomandibular joint osteoarthritis (TMJ OA) is characterized by progressive degeneration of the fibrocartilaginous articular surface. We previously demonstrated that combined bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) inhibition promotes endogenous hyaline cartilage regeneration in appendicular joints. Whether this regenerative strategy can be extended to the specialized fibrocartilage of the TMJ remains unknown. In this study, we evaluated the regenerative potential of BMP-2 combined with cabozantinib, an FDA-approved multikinase inhibitor with activity against VEGF receptors, using complementary murine and porcine TMJ cartilage injury models. In mice, needle-induced abrasion of the mandibular condyle resulted in loss of the fibrocartilaginous articular surface and extracellular matrix; treatment with BMP-2 and cabozantinib was associated with improved cartilage architecture and increased fibrocartilage thickness. To examine translational feasibility, we developed a surgically accessible porcine TMJ cartilage defect model and demonstrated the technical feasibility of local BMP-2 and cabozantinib delivery with formation of repair tissue within the defect. Collectively, these findings provide preliminary evidence supporting further investigation of combined BMP-2 and cabozantinib for TMJ cartilage repair.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nahir Rodríguez-Costas, Arturo Rodríguez-Blanco, Cristina Regueiro Expósito, Joaquín Cubiella, Esteban Sinde Stompel, Catalina Fernández-de-Ana Portela, Astrid Irene Diez Martín, Pablo Taboada-Rodríguez, Belén Fontán Silva, María Dolores Rodríguez Fernández, Sara Zarraquiños, David Remedios, Cristina Alejandra Sánchez Gómez, Sara Alonso Lorenzo, Romina Fernández Poceiro, María Luisa de Castro Parga, Vicent Hernández Ramírez, Sonia Pérez-Castro
{"title":"Beyond Taxonomy: Fungal Nutraceutical Supplementation Modifies the Functional Potential of the Gut Microbiome in Colorectal Cancer.","authors":"Nahir Rodríguez-Costas, Arturo Rodríguez-Blanco, Cristina Regueiro Expósito, Joaquín Cubiella, Esteban Sinde Stompel, Catalina Fernández-de-Ana Portela, Astrid Irene Diez Martín, Pablo Taboada-Rodríguez, Belén Fontán Silva, María Dolores Rodríguez Fernández, Sara Zarraquiños, David Remedios, Cristina Alejandra Sánchez Gómez, Sara Alonso Lorenzo, Romina Fernández Poceiro, María Luisa de Castro Parga, Vicent Hernández Ramírez, Sonia Pérez-Castro","doi":"10.3390/ijms27198936","DOIUrl":"10.3390/ijms27198936","url":null,"abstract":"<p><p>The gut microbiome is increasingly recognized as an important determinant of host immune regulation, intestinal homeostasis, and recovery after colorectal cancer (CRC) surgery. Although our previous randomized, double-blind, placebo-controlled clinical trial demonstrated that fungal nutraceutical supplementation with Micodigest<sup>®</sup> was associated with favorable taxonomic and systemic inflammatory changes in patients undergoing CRC surgery with curative intent, the functional consequences of this intervention remain poorly understood. Here, we performed a functional metagenomic analysis of fecal samples collected from patients enrolled in the original clinical trial to investigate whether Micodigest<sup>®</sup> supplementation was associated with changes in the functional potential of the gut microbiome. A total of 37 patients were analyzed, including 24 receiving Micodigest<sup>®</sup> and 13 receiving placebo, with paired samples collected before supplementation and after 4-6 weeks of intervention. Shallow shotgun metagenomic sequencing was performed, and microbial functional potential was characterized using KEGG Orthologues (KOs). Differential abundance analysis identified 14 significantly different KOs between groups at baseline and 23 after intervention, with no overlap between the two sets of orthologues. Following supplementation, Micodigest<sup>®</sup>-treated patients exhibited increased representation of functions related to CRISPR-associated systems, bacteriophage biology, and chitin-derived carbohydrate utilization, together with reduced representation of nutrient acquisition systems, conjugative transfer, sulfur metabolism, and components of the Wood-Ljungdahl pathway. These functional signatures suggest coordinated changes in microbial ecological adaptation, nutrient utilization, genetic exchange, and metabolic activity following fungal nutraceutical supplementation. Integration with previously reported taxonomic and inflammatory findings supports the hypothesis that Micodigest<sup>®</sup> may promote coordinated remodeling of the gut microbiome and host-microbiota interactions during the perioperative period. Although the present study cannot establish causality or directly infer microbial activity from metagenomic potential, these findings provide novel functional insights into the microbiome response to fungal nutraceutical supplementation in patients with CRC and highlight functional metagenomics as a valuable complement to taxonomic profiling.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wojciech Kupczyk, Joanna Boinska, Artur Słomka, Kinga Kupczyk, Marek Jackowski, Ewa Żekanowska
{"title":"Changes in Isthmin-1, Irisin, and the AGE-RAGE Axis Following LSG: A Prospective Single-Center Cohort Study.","authors":"Wojciech Kupczyk, Joanna Boinska, Artur Słomka, Kinga Kupczyk, Marek Jackowski, Ewa Żekanowska","doi":"10.3390/ijms27198932","DOIUrl":"10.3390/ijms27198932","url":null,"abstract":"<p><p>This prospective single-center cohort study evaluated changes in serum levels of novel adipokines and myokines, including isthmin-1 and irisin, as well as the advanced glycation end product (AGE)-soluble receptor for AGE (sRAGE) axis and monomeric C-reactive protein (mCRP) in patients with obesity before and 5 months after laparoscopic sleeve gastrectomy (LSG). The study included 38 patients with obesity (26 females and 12 males) with a median age of 42 years who underwent LSG. Laboratory parameters were assessed using commercially available immunoenzymatic assays. We observed a significant decrease in isthmin-1 concentration at the postoperative time point (Me = 2.10 ng/mL vs. Me = 1.93 ng/mL, <i>p</i> = 0.009). Moreover, a significant increase in irisin levels (Me = 7.33 µg/mL vs. Me = 10.64 µg/mL, <i>p</i> = 0.002) and AGEs (Me = 589.50 ng/mL vs. Me = 698.60 ng/mL, <i>p</i> = 0.015) was observed after LSG. A significant increase in AGE levels was also noted after normalization to total protein (Me = 8.34 ng/mg protein vs. Me = 10.37 ng/mg protein, <i>p</i> = 0.027). sRAGE levels were similar at both time points. Five months after LSG, mCRP levels were significantly lower (Me = 1.99 ng/mL vs. Me = 1.55 ng/mL, <i>p</i> = 0.020). Exploratory correlation analyses identified potential associations between AGEs and isthmin-1 (R = 0.37) and between sRAGE and irisin (R = -0.31) preoperatively. Five months after LSG, potential associations were observed between AGEs and irisin (R = 0.38) and between sRAGE and mCRP (R = -0.37). Our findings indicate a decrease in circulating isthmin-1 and mCRP, together with an increase in irisin and AGE concentrations following LSG, suggesting changes in selected metabolic and tissue-related biomarkers after surgery. Further studies are needed to determine the mechanisms underlying these changes and to clarify their potential clinical significance.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manjit Panigrahi, Divya Rajawat, Amritanshu Upadhyay, K Devadharshini, G Ranjith, Pratik Kumar Rath, Surya Kant Verma, Sonali Sonejita Nayak
{"title":"Mito-Nuclear Interactions in Livestock: Implications for Adaptation, Productivity, and Precision Breeding.","authors":"Manjit Panigrahi, Divya Rajawat, Amritanshu Upadhyay, K Devadharshini, G Ranjith, Pratik Kumar Rath, Surya Kant Verma, Sonali Sonejita Nayak","doi":"10.3390/ijms27198921","DOIUrl":"10.3390/ijms27198921","url":null,"abstract":"<p><p>Mitochondria are central regulators of cellular energy metabolism, stress responses, and physiological adaptation, with their functions depending on the coordinated interaction between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). These mito-nuclear interactions are essential for maintaining oxidative phosphorylation (OXPHOS), cellular homeostasis, and overall organismal fitness. Increasing evidence suggests that mito-nuclear compatibility influences a wide range of economically important traits in livestock, including growth, milk production, reproduction, feed efficiency, disease resistance, and environmental adaptation. This review provides a comprehensive overview of mitochondrial and nuclear genome organization, mechanisms of mito-nuclear communication, and their biological significance in livestock species. Key mechanisms discussed include mito-nuclear co-evolution, anterograde and retrograde signaling, reactive oxygen species (ROS)-mediated signaling, epigenetic regulation, mitophagy, mitochondrial biogenesis, and mito-nuclear incompatibility. The review further highlights the role of mito-nuclear interactions in adaptation to heat stress, high-altitude environments, metabolic challenges, and disease resistance, as well as their influence on productivity traits such as milk yield, growth performance, fertility, reproductive efficiency, and longevity. Advances in genomic and multi-omics technologies, including genome-wide association studies (GWAS), mitogenomics, transcriptomics, proteomics, metabolomics, single-cell omics, network biology, and systems genomics, have greatly enhanced our understanding of mitochondrial function and its contribution to complex traits. Furthermore, integrating mitochondrial information into genomic selection, marker-assisted breeding, climate-smart livestock improvement, and precision livestock farming (PLF) offers new opportunities to enhance productivity, resilience, and sustainability. Understanding the genetic and functional basis of mito-nuclear interactions will facilitate the development of next-generation precision breeding strategies aimed at improving livestock performance under changing environmental conditions.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marc Andreu-Inglés, Alina-Iuliana Onoiu, Marc Grifoll-Escoda, Anna Hernández-Aguilera, Josep Gumà-Padró, Francesc Riu, Karla Peña, Jordi Camps, David Parada
{"title":"Urinary DNA Methylation Profiling Identifies a Biologically Distinct Subgroup of Low-Grade Urothelial Carcinoma with High-Grade-Associated Features.","authors":"Marc Andreu-Inglés, Alina-Iuliana Onoiu, Marc Grifoll-Escoda, Anna Hernández-Aguilera, Josep Gumà-Padró, Francesc Riu, Karla Peña, Jordi Camps, David Parada","doi":"10.3390/ijms27198934","DOIUrl":"10.3390/ijms27198934","url":null,"abstract":"<p><p>Bladder cancer surveillance remains challenging because conventional methods do not fully capture the biological heterogeneity within histologically low-grade urothelial carcinoma (LGUC). We evaluated whether urinary DNA methylation profiling using Bladder EpiCheck™ can identify clinically relevant LGUC subgroups in a retrospective single-center cohort of 134 patients with paired histopathology, urine cytology, and methylation results. Methylation positivity increased across negative histopathology, LGUC, and high-grade urothelial carcinoma (HGUC) (18.4%, 51.4%, and 91.5%, respectively). Within LGUC, 19 of 37 tumors (51.4%) were methylation-positive. Their EpiScores overlapped those of HGUC, whereas methylation-negative LGUCs exhibited scores similar to negative histopathology. Gaussian mixture modeling independently supported a bimodal distribution. Methylation-positive LGUCs demonstrated a higher Ki67 labeling index, more frequent MTAP loss (33.3% vs. 11.8%), and more recurrences, including recurrence as HGUC, than methylation-negative LGUCs. Conventional nuclear morphometry did not distinguish between the two LGUC subgroups. These exploratory findings suggest that urinary DNA methylation may identify a biologically distinct subset of histologically low-grade tumors with selected high-grade-associated features. Prospective external validation is required before methylation status can inform surveillance or treatment decisions.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inês Fortuna, Janete Santos, Paula Soeiro, Raquel Machado, Ana Oliveira, Jorge Pereira, Giuseppe Limongelli, Teresa Faria, Elisabete Martins
{"title":"Tracking Active Fibroblast-Mediated Tissue Remodelling in Cardiomyopathies: Translational Insights from FAPI PET Imaging.","authors":"Inês Fortuna, Janete Santos, Paula Soeiro, Raquel Machado, Ana Oliveira, Jorge Pereira, Giuseppe Limongelli, Teresa Faria, Elisabete Martins","doi":"10.3390/ijms27198901","DOIUrl":"10.3390/ijms27198901","url":null,"abstract":"<p><p>Myocardial fibrosis is a major pathological component of cardiac remodelling and contributes to ventricular stiffness, impaired myocardial function, heart failure progression, and arrhythmic vulnerability across a broad spectrum of cardiomyopathies. In hypertrophic cardiomyopathy (HCM), fibrotic remodelling encompasses both diffuse interstitial matrix expansion and focal replacement fibrosis and is closely associated with disease severity and adverse clinical outcomes. Cardiac magnetic resonance (CMR), using late gadolinium enhancement (LGE) and quantitative parametric mapping, is central to non-invasive myocardial tissue characterization. LGE primarily identifies focal areas of replacement fibrosis and scar, whereas native T1, T2, and extracellular volume (ECV) mapping provide complementary information on diffuse myocardial and interstitial tissue abnormalities, including extracellular matrix expansion. However, these techniques characterize the structural and tissue-level consequences of myocardial injury and remodelling rather than directly visualizing the cellular processes underlying fibroblast activation. Fibroblast activation protein inhibitor positron emission tomography (FAPI PET) has emerged as a promising molecular imaging approach for assessing active fibroblast-mediated tissue remodelling. By targeting fibroblast activation protein (FAP), a cell-surface serine protease upregulated in activated fibroblasts and myofibroblasts. FAPI radiotracers may provide a molecular readout of accessible FAP expression that complements structural and tissue characterization by CMR. This review examines the cellular and molecular mechanisms underlying active myocardial remodelling, with particular emphasis on transforming growth factor-β1 (TGF-β1)/Smad signalling, fibroblast-to-myofibroblast transition, FAP expression, and extracellular matrix turnover. We critically evaluate the current clinical evidence for FAPI PET/CT and hybrid PET/CMR across cardiomyopathies, focusing on HCM while also considering ischemic, inflammatory, infiltrative, and other non-ischemic forms of cardiac remodelling. Particular attention is given to the relationship between myocardial FAPI uptake, CMR tissue characterization, ventricular function, circulating biomarkers, and calculated arrhythmic risk. Although initial studies support the complementary value of FAPI PET and CMR for characterizing active and established myocardial remodelling, the available evidence remains limited by small, predominantly single-centre cohorts, heterogeneous radiotracers and acquisition protocols, and the absence of validated quantitative thresholds or prospective outcome data. Larger longitudinal studies are required to determine whether FAPI PET can provide incremental prognostic information or serve as a reproducible imaging biomarker for disease progression and therapeutic response.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anastasia Gurina, Anna Margarit, Anastasia Zhikhreva, Nadezhda Frolova, Andrej Frolov
{"title":"Multiomics Insights in Research of Nitric Oxide (NO) Donors in Plants upon Stress.","authors":"Anastasia Gurina, Anna Margarit, Anastasia Zhikhreva, Nadezhda Frolova, Andrej Frolov","doi":"10.3390/ijms27198897","DOIUrl":"10.3390/ijms27198897","url":null,"abstract":"<p><p>It is known that the progressive climate changes and environmental pollution prevalent all over the world lead to increasingly frequent and prolonged episodes of stress, and it challenges plants to adapt to changing adverse conditions. Given the significant crop losses caused by challenging environments, protecting plants from the destructive effects of these factors has become one of the most pressing challenges in modern agricultural biology and plant physiology. One of the approaches to protect plants from stressors in modern agrobiotechnology is the use of nitric oxide (NO) donors, which are chemicals that can release NO in plant cells and stimulate their germination, growth, biomass accumulation, and protection against external factors. Studying their mechanism of action at the molecular level is essential for understanding the targets of NO action, as well as for developing new phytoeffectors. A multiomics approach, along with physiological data, is often the method of choice. In this review, we compare widely used NO donors (e.g., sodium nitroprusside, <i>S</i>-nitrosoglutathione, NONOates) in terms of chemical properties, NO-release kinetics, stability, and suitability for different application methods (seed treatment, foliar spray, root application). Finally, we highlight recent advances from proteomics, metabolomics, and transcriptomics that have enabled system-wide identification of NO-responsive pathways and candidate targets. By integrating physiological, biochemical, and multiomics data, this review provides a framework for understanding NO-mediated stress tolerance and for the rational design of new NO-based phytoeffectors.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irina V Zhigacheva, Elena M Mil, Irina F Rusina, Natalya I Krikunova, Ludmila I Matienko, Timur L Veprintsev, Anastasia A Albantova, Alexander N Goloshchapov
{"title":"Biological Activity of 3-Hydroxypyridine Derivatives with Natural Components.","authors":"Irina V Zhigacheva, Elena M Mil, Irina F Rusina, Natalya I Krikunova, Ludmila I Matienko, Timur L Veprintsev, Anastasia A Albantova, Alexander N Goloshchapov","doi":"10.3390/ijms27198903","DOIUrl":"10.3390/ijms27198903","url":null,"abstract":"<p><p>We investigated the antiradical properties of antioxidants: carnitinate 2-ethyl-6-methyl-3-hydroxypyridine (CAR-3-HP) and carboxychromate-2-ethyl-6-methyl-3-hydroxypyridine (CCR-3-HP), and also assessed the mitochondrial response to stress (hypoxia) by analyzing the intensity of lipid peroxidation, membrane fatty acid composition, and activation of autophagy markers LC3 and Beclin-1 using spectrofluorimetry, chromatography, and immunoblotting, respectively. The studied antioxidants exhibited high antiradical activity, which was reflected in their ability to inhibit lipid peroxidation. Five-day administration of antioxidants to mice at a dose of 2 × 10<sup>-9</sup> mol/kg prevented the activation of lipid peroxidation in liver mitochondrial membranes under conditions of acute hypobaric hypoxia. The drugs also prevented a decrease in C<sub>18</sub> and C<sub>20</sub> fatty acid levels, and also activated autophagy. In both cases, CAR-3-HP was more effective than CCR-3-HP. This drug increased the lifespan of mice almost twice as effectively under conditions of various types of hypoxias.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Organ-Specific Phenolic Specialization and Antioxidant Responses in <i>Crocus cancellatus</i>: LC-MS/MS and Multivariate Analysis.","authors":"Bedrettin Selvi","doi":"10.3390/ijms27198904","DOIUrl":"10.3390/ijms27198904","url":null,"abstract":"<p><p>Organ-specific allocation of phenolic metabolites may shape antioxidant responses in <i>Crocus</i> species. This study characterized stamen, pistil, tepal, perigon tube, and corm of <i>Crocus cancellatus</i> Herb. using ultrasound-assisted methanolic extraction, liquid chromatography-tandem mass spectrometry with 30 authentic standards, six antioxidant assays, a relative antioxidant capacity index, Pearson correlation analysis, and principal component analysis. Twenty phenolic compounds were quantified. Hesperidin predominated in all organs and was highest in the tepal (17,660 ± 60 μg/g extract), approximately 43-fold above the corm. The pistil contained the highest 3-hydroxybenzoic acid (331 ± 1 μg/g extract) and 4-hydroxybenzoic acid (341 ± 2 μg/g extract), whereas the corm was enriched in pinoresinol (60.1 ± 0.8 μg/g extract) and uniquely contained vanillin (16.0 ± 0.6 μg/g extract). The tepal showed the highest total flavonoid content (81.50 ± 0.40 mg RE/g extract), while the stamen had the highest total phenolic content (12.63 ± 0.05 mg GAE/g extract). The corm showed the strongest DPPH radical scavenging (IC<sub>50</sub> = 3.96 mg/mL), whereas the pistil led in ABTS and FRAP responses. Principal component analysis explained 64.16% of total variance and separated the five organ profiles. These findings demonstrate organ-specific phenolic specialization and support targeted bioactivity studies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}