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32 pages, 76631 KB  
Review
TOR Signaling as a Central Integrator of Embryogenic Reprogramming During 2,4-D-Induced Somatic Embryogenesis
by José Luis Cabrera-Ponce, Alex Ricardo Bermudez-Valle, Maria del Rosario Cárdenas-Aquino, Andrea Maria Navarro-Vega, Braulio Uribe-Lopez, Aaron Barraza-Celis, Eliana Valencia-Lozano and Lisset Herrera-Isidron
Int. J. Mol. Sci. 2026, 27(14), 6191; https://doi.org/10.3390/ijms27146191 - 10 Jul 2026
Abstract
2,4-Dichlorophenoxyacetic acid (2,4-D), originally developed as a synthetic auxinic herbicide, is the most widely used chemical inducer of somatic embryogenesis (SE) in plants. Despite extensive use of 2,4-D in plant regeneration, the systems-level regulatory mechanisms connecting hormonal signaling, metabolic reprogramming, translational control, and [...] Read more.
2,4-Dichlorophenoxyacetic acid (2,4-D), originally developed as a synthetic auxinic herbicide, is the most widely used chemical inducer of somatic embryogenesis (SE) in plants. Despite extensive use of 2,4-D in plant regeneration, the systems-level regulatory mechanisms connecting hormonal signaling, metabolic reprogramming, translational control, and embryogenic competence remain poorly resolved. Here, we hypothesize that TOR signaling functions as an integrative molecular hub coordinating transcriptional, metabolic, and developmental reprogramming during somatic embryogenesis induction. To investigate the molecular regulatory landscape associated with 2,4-D-induced SE, we performed a systems-level analysis integrating publicly available transcriptomic data from Arabidopsis thaliana with high-confidence protein–protein interaction (PPI) network analyses using STRING v12.0 (confidence score ≥ 0.900). Using a previously published transcriptomic dataset, we identified 1927 upregulated genes associated with SE induction, which were organized into 34 functional modules related to transcriptional regulation, translation metabolism, hormone signaling and cellular homeostasis. Within this interactome, TARGET OF RAPAMYCIN (TOR) kinase emerged as an integrative regulatory hub associated with multiple pathways involved in embryogenic reprogramming. Network analyses revealed three major TOR-associated regulatory axes: (1) the TOR–FKBP12–RPS6A axis, associated with ribosome biogenesis and translational regulation; (2) the TOR–CBP20 axis, connected with transcriptional reprogramming; SE master regulators (LEC1, LEC2, and FUS3); and lipid, sterol, brassinosteroid (BR), and auxin-associated pathways; and (3) the TOR–TAP46 axis, linked with one-carbon metabolism, nucleotide biosynthesis, DNA replication and repair, and genome-stability pathways. Additionally, the network contained 411 embryo-lethal (EMBL) genes distributed across multiple regulatory modules, reinforcing the biological relevance of the identified interactome and highlighting the importance of coordinated developmental, metabolic, and transcriptional regulation during embryogenesis induction. These findings support a systems-level TOR-associated regulatory framework involved in the integration of transcriptional, translational, metabolic, hormonal, and genome-maintenance pathways during embryogenesis. This interactome model provides a foundation for functional studies aimed at dissecting the molecular mechanisms underlying SE and identifying candidate targets to improve regeneration and biotechnological application and crop genetic engineering. Collectively, this study proposes a mechanistic framework in which TOR signaling integrates developmental, metabolic, translational, and genome-stability pathways to orchestrate embryogenic competence, providing candidate molecular targets for improving plant regeneration and genome engineering platforms. Full article
(This article belongs to the Section Molecular Biology)
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18 pages, 4545 KB  
Article
LcCOL7 and LcCOL8 Negatively Regulate Plant Flowering Independent of Day Length
by Tingting Yan, Yukun He, Tianyi Tang, Haida Deng, Ding Chen, Farhat Abbas, Zhe Chen, Mingchao Yang, Xianghe Wang and Fuchu Hu
Plants 2026, 15(14), 2139; https://doi.org/10.3390/plants15142139 - 10 Jul 2026
Abstract
CONSTANS-LIKE (COL) genes are pivotal regulatory components in the photoperiodic flowering pathway of plants. These genes can be regulated by both photoreceptors and the circadian clock, modulating plant flowering responses under specific day lengths by regulating florigen levels. However, the COL [...] Read more.
CONSTANS-LIKE (COL) genes are pivotal regulatory components in the photoperiodic flowering pathway of plants. These genes can be regulated by both photoreceptors and the circadian clock, modulating plant flowering responses under specific day lengths by regulating florigen levels. However, the COL gene family in Litchi chinensis Sonn. has not yet been characterized. In this study, we identified eight COL family members in litchi and classified them into three subgroups based on phylogenetic analysis. The analysis of cis-regulatory elements within the promoters of LcCOLs revealed a wide distribution of elements associated with light, hormone, and stress responses. Transcript expression profiling indicated that most LcCOLs exhibited relatively high expression levels in leaf buds, leaves, and young fruits. Diurnal expression analysis under natural photoperiod conditions revealed that the expression peaks of all LcCOLs, with the exception of LcCOL1, occurred during the nighttime. The heterologous overexpression of LcCOL7 and LcCOL8, the closest homologs to AtCO, in Arabidopsis thaliana significantly delayed the flowering time under both long-day (LD) and short-day (SD) conditions, indicating that these genes act as repressors of flowering. This study provides a foundational basis for elucidating the molecular mechanisms underlying litchi flowering regulation and identifies promising candidate genes for the molecular breeding of litchi flowering-related agronomic traits. Full article
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28 pages, 364 KB  
Review
Food Safety Standards, Regulatory Paradigms, and International Trade Between the European Union, the United States, and Other Major Commercial Blocs
by Fernando Mata, Meirielly Jesus and Joana Santos
Sci 2026, 8(7), 166; https://doi.org/10.3390/sci8070166 - 10 Jul 2026
Abstract
Global food trade exposes sharp differences in food safety regulation, especially between the EU and the US. The EU follows a precautionary, hazard-based model, allowing intervention under scientific uncertainty to protect consumers, maintain public trust, and avoid long-term risks. The US applies a [...] Read more.
Global food trade exposes sharp differences in food safety regulation, especially between the EU and the US. The EU follows a precautionary, hazard-based model, allowing intervention under scientific uncertainty to protect consumers, maintain public trust, and avoid long-term risks. The US applies a science-based, proof-of-harm approach, requiring clearer evidence of risk before limiting market access, supporting innovation and regulatory efficiency. These contrasting philosophies create trade tensions and non-tariff barriers, as seen in disputes over hormone-treated beef, genetically modified organisms, and chlorine-washed poultry. Beyond the transatlantic context, countries adopt precautionary, science-based, or hybrid systems depending on domestic priorities, institutional capacity, and trade commitments. Hybrid models in India, China, and parts of Africa combine precautionary safeguards with evidence-based risk assessment to balance consumer protection and market access. International bodies such as Codex Alimentarius, the WHO, and the WTO help manage regulatory divergence through standards, guidance, and dispute resolution, while recognising precaution under uncertainty. Recent EU agreements with Mercosur and India show pragmatic cooperation through transparency, safeguards, and sanitary and phytosanitary commitments. Overall, effective global food governance depends on hybrid, coordinated, and adaptive approaches that reconcile health protection, trade facilitation, and innovation. Full article
27 pages, 2151 KB  
Review
Endothelial Mitochondrial Dysfunction in INOCA and Coronary Microvascular Dysfunction: Mechanisms, Sex Differences, and Therapeutic Implications
by Roko Santic, Lovre Martinovic, Marko Kumric, Nikola Pavlovic, Dinko Martinovic, Lovre Jukic, Zenon Pogorelic and Josko Bozic
J. Cardiovasc. Dev. Dis. 2026, 13(7), 321; https://doi.org/10.3390/jcdd13070321 - 10 Jul 2026
Abstract
Ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) are increasingly recognized causes of angina, reduced quality of life, and elevated cardiovascular risk, yet mechanistic heterogeneity complicates diagnosis and treatment. This narrative review synthesizes evidence from clinical guidelines, consensus documents, landmark [...] Read more.
Ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) are increasingly recognized causes of angina, reduced quality of life, and elevated cardiovascular risk, yet mechanistic heterogeneity complicates diagnosis and treatment. This narrative review synthesizes evidence from clinical guidelines, consensus documents, landmark trials, cohorts, mechanistic studies, and high-quality reviews identified through structured, non-exhaustive searches of PubMed/MEDLINE, Google Scholar, and major cardiovascular society documents. Current evidence indicates that endothelial mitochondria function primarily as signaling organelles, regulating reactive oxygen species, nitric oxide bioavailability, endothelium-dependent hyperpolarization, calcium signaling, inflammatory activation, mitophagy, and endothelial survival. Cardiometabolic risk factors, aging, chronic kidney disease, and postmenopausal hormonal changes may converge on mitochondrial quality-control and redox pathways, contributing to CMD susceptibility and sex-specific vulnerability. However, direct human evidence linking endothelial mitochondrial dysfunction causally to CMD defined by invasive coronary function testing remains limited. Coronary physiological testing and acetylcholine provocation are validated tools for CMD endotyping, whereas mitochondrial biomarkers remain investigational. Endotype-guided diagnosis and management remain central, while mitochondria-targeted strategies require prospective CMD-specific validation. Full article
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28 pages, 2581 KB  
Review
Gut Microbiota and Metabolic Syndrome: A Narrative Review
by Ioanna Kotsiri, Maria Prokou, Charalampia Melangeli Domazinaki, Eirini Papadakaki and Emmanouil Magiorkinis
Biology 2026, 15(14), 1115; https://doi.org/10.3390/biology15141115 - 10 Jul 2026
Abstract
Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial [...] Read more.
Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut–brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases. Full article
(This article belongs to the Section Medical Biology)
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16 pages, 16681 KB  
Article
Genome-Wide Characterization of the Homeodomain-Leucine Zipper (HD-Zip) III Gene in Brassica juncea L. and Its Expression During Axillary Bud Development
by Yuling Zhang, Huanhuan Jiang, Jia Li, Lulu Wang, Fenghao Liang, Lihong Dai, Bin Yang, Rong Tang, Shaolin Lei, Huagui Xiao, Yuan Tao and Chao Zhang
Agronomy 2026, 16(14), 1319; https://doi.org/10.3390/agronomy16141319 - 10 Jul 2026
Abstract
HD-Zip III transcription factors are known to play roles in regulating shoot apical meristem (SAM) and axillary meristem (AM) development, exerting direct effects on plant architecture and branching. However, the HD-Zip III (BjuHDZ) gene family has not been systematically characterized in [...] Read more.
HD-Zip III transcription factors are known to play roles in regulating shoot apical meristem (SAM) and axillary meristem (AM) development, exerting direct effects on plant architecture and branching. However, the HD-Zip III (BjuHDZ) gene family has not been systematically characterized in Brassica juncea L. (B. juncea). Therefore, in this study, we performed a comprehensive bioinformatics analysis of the BjuHDZ gene family and identified a total of 20 members. These genes were randomly and unevenly distributed across the 16 chromosomes of B. juncea, and their encoded proteins exhibited divergent physicochemical properties. Through phylogenetic analysis, the 20 BjuHDZ proteins were divided into five subgroups (REV, HB8, HB9, HB14, and HB15). Conserved exon–intron organization and motif profiles were observed within each BjuHDZ gene subgroup. Furthermore, their promoter sequences harbored a wide array of cis-elements implicated in light responsiveness, hormonal regulation, stress tolerance, and growth/development. The qRT-PCR analysis showed that the expression levels of BjuHDZ7, BjuHDZ13, and BjuHDZ15 were significantly upregulated in the middle and upper axillary buds of two pairs of multi-branching (Bj02 and, Bj08) accessions. Meanwhile, BjuHDZ17 was highly expressed in the upper, middle, and lower axillary buds as well as in the SAM of both multi-branching materials. Taken together, these findings lay a foundation for further investigation into the biological functions of BjuHDZ genes in B. juncea. Full article
(This article belongs to the Section Crop Breeding and Genetics)
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15 pages, 2887 KB  
Article
TaPIK3AP Regulates Female Reproduction in Tuta absoluta Through Juvenile Hormone-, Vitellogenin-, and TOR-Related Signaling
by Jing Li, Jiahui Song, Li Yang, Zhuting Zhang, Guy Smagghe and Wenjia Yang
Insects 2026, 17(7), 711; https://doi.org/10.3390/insects17070711 - 10 Jul 2026
Abstract
Tuta absoluta is a globally significant invasive pest that has rapidly developed resistance to multiple classes of insecticides, highlighting the critical need for RNA interference (RNAi) targets for sustainable pest management. The insulin signaling pathway is a key regulator of insect reproduction; however, [...] Read more.
Tuta absoluta is a globally significant invasive pest that has rapidly developed resistance to multiple classes of insecticides, highlighting the critical need for RNA interference (RNAi) targets for sustainable pest management. The insulin signaling pathway is a key regulator of insect reproduction; however, the role of PIK3AP, an adaptor protein that links receptor tyrosine kinases to the PI3K-Akt signaling pathway, remains poorly understood in Lepidopteran pests. In this study, TaPIK3AP was identified in T. absoluta, exhibiting elevated expression levels in the heads of female adults and during the early reproductive period. RNAi-mediated knockdown of TaPIK3AP reduced fecundity by 76%, decreased egg hatching rate by 43%, shortened the oviposition period by two days, and caused pronounced ovarian atrophy accompanied by impaired yolk deposition. Mechanistically, knockdown of TaPIK3AP led to the suppression of Vg and VgR expression, a reduction in juvenile hormone (JH) titer, downregulation of JH signaling genes, and a significant decrease in the transcript levels of key components of the target of rapamycin (TOR) pathway, including mTOR, Rheb, and S6K. These findings demonstrate that TaPIK3AP integrates Vg, JH, and TOR signaling pathways to regulate female reproduction in T. absoluta, thereby identifying it as a potential molecular target for RNAi-based sustainable pest management strategies. Full article
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19 pages, 6058 KB  
Article
Identification and Expression Profile of the Chalcone Synthase (CHS) Gene Family in Litchi
by Yunmei Li, Ranran Li, Jincan Xiao, Yuhao Liu, Ding Fan, Jiongzhi Xu, Wenhui Yang, Haifeng Jia and Haiji Qiu
Int. J. Mol. Sci. 2026, 27(14), 6152; https://doi.org/10.3390/ijms27146152 - 9 Jul 2026
Abstract
The chalcone synthase (CHS) genes play an important role in the biosynthesis of flavonoids and anthocyanins. However, research into the genomic characteristics and evolutionary patterns of the CHS gene family in lychee remains limited. In this study, six LcCHS genes were [...] Read more.
The chalcone synthase (CHS) genes play an important role in the biosynthesis of flavonoids and anthocyanins. However, research into the genomic characteristics and evolutionary patterns of the CHS gene family in lychee remains limited. In this study, six LcCHS genes were identified from the litchi genome. Most members of the LcCHS family consist of two exons and possess eight conserved motifs; furthermore, all members exhibit highly similar three-dimensional protein structures. LcCHS genes were closely related to homologs of Sapindaceae species and experienced gene duplication events during dicotevolution. Comparative colinearity analysis revealed conserved colinearity relationships among most LcCHS genes, and all members of the LcCHS family exhibited distinct colinearity with homologues in longan. LcCHS genes exhibited significant tissue-specific expression preferentially in reproductive tissues rather than vegetative tissues. Transcription analysis of ‘Jinggang Hongnuo’ litchi fruit development divided LcCHS genes into two negatively correlated expression modules and LcCHS members interacted with numerous transcription factors (e.g., flavonoid biosynthesis, hormone signaling and developmental regulation). Spatiotemporal expression profiling of LcCHS genes in ‘Guiwei’, ‘Feizixiao’ and ‘Ziniangxi’ litchi cultivars revealed obvious tissue specificity and developmental stage preference of these genes. Gene expression of LcCHS genes in ‘Guiwei’ high correlated with the flavonoid content. Furthermore, promoter cis-element analysis identified 34 types of cis elements in LcCHS promoters that participate in plant growth and development, hormone response and stress adaptation, implying that LcCHS genes may participate in litchi growth, hormone signal transduction, and stress-response processes. Comprehensive characterization of the chalcone synthase gene family could provide insights into the genetic improvement of litchi. Full article
(This article belongs to the Section Molecular Plant Sciences)
31 pages, 1305 KB  
Review
Tomato Leaf Color Diversity as a Functional Trait: Molecular Mechanisms, Physiological Significance, and Environmental Responses
by Rahmatullah Jan, Shahzad Iqbal, Sajad Ali and Kyung-Min Kim
Int. J. Mol. Sci. 2026, 27(14), 6151; https://doi.org/10.3390/ijms27146151 - 9 Jul 2026
Abstract
Leaf color in tomato (Solanum lycopersicum L.) is a complex and highly informative trait that reflects pigment metabolism, chloroplast development, genetic regulation, hormonal signaling, and environmental influences. This review synthesizes current knowledge on the biological basis and diversity of tomato leaf coloration, [...] Read more.
Leaf color in tomato (Solanum lycopersicum L.) is a complex and highly informative trait that reflects pigment metabolism, chloroplast development, genetic regulation, hormonal signaling, and environmental influences. This review synthesizes current knowledge on the biological basis and diversity of tomato leaf coloration, with a particular focus on the roles of chlorophylls, carotenoids, anthocyanins, and flavonoids in generating distinct visual phenotypes. It further discusses the molecular and physiological mechanisms associated with key leaf color types, including dark green, pale green, chlorotic, purple, albino, and variegated leaves, and describes how these phenotypes develop through coordinated regulation of pigment biosynthesis, chloroplast biogenesis, and stress-responsive pathways. The review also summarizes the effects of environmental factors such as light, temperature, water availability, nutrient status, salinity, heavy metals, and biotic stress on leaf pigmentation through changes in photosynthetic efficiency and oxidative balance. In addition, hormonal regulation of leaf color is discussed with emphasis on the roles of abscisic acid (ABA), ethylene (ET), cytokinins (CKs), auxins, jasmonic acids (JA), and salicylic acid (SA) in regulating chlorophyll retention and senescence-associated color transitions. Importantly, leaf coloration functions not only as a morphological trait but also as a sensitive biomarker of plant physiological status, enabling early detection of nutrient deficiencies, abiotic stress, and disease. Recent advances in multi-omics approaches, imaging technologies, and machine learning have significantly improved the understanding of the regulatory networks controlling leaf pigmentation and their relationship with crop performance. However, important gaps remain in integrating molecular mechanisms with whole-plant and field-level responses. Future progress will depend on combining systems biology, high-throughput phenotyping, and predictive modeling to translate leaf color studies into practical applications for improving tomato productivity, stress resilience, and climate adaptation. Full article
(This article belongs to the Section Molecular Plant Sciences)
16 pages, 10534 KB  
Article
The bHLH Transcription Factor IbbHLH129 Positively Regulates the Cold Tolerance of Sweetpotato Seedlings by Modulating Auxin and Gibberellin Pathways
by Jiaquan Pan, Zitong Yang, Sitong Liu, Zhenlei Liu and Tao Yu
Plants 2026, 15(14), 2123; https://doi.org/10.3390/plants15142123 - 9 Jul 2026
Abstract
Low-temperature stress severely inhibits the growth and development of sweetpotato, restricts its planting geographical range, and frequently causes seedling death and yield reduction, posing a major threat to sweetpotato sustainable production. Nevertheless, the molecular regulatory mechanisms by which sweetpotato perceives and adapts to [...] Read more.
Low-temperature stress severely inhibits the growth and development of sweetpotato, restricts its planting geographical range, and frequently causes seedling death and yield reduction, posing a major threat to sweetpotato sustainable production. Nevertheless, the molecular regulatory mechanisms by which sweetpotato perceives and adapts to low-temperature stress have not been fully elucidated and deserve further in-depth investigation. In this study, a basic helix–loop–helix (bHLH) transcription factor IbbHLH129 was cloned from a cold-tolerant sweetpotato variety Xs33. The IbbHLH129 protein is localized in the nucleus. IbbHLH129 is most highly expressed in sweetpotato leaves and upregulated by low temperature, GA3, MeJA, and IAA, while repressed by ABA. Overexpressing IbbHLH129 enhanced cold tolerance in sweetpotato seedlings under short-term cold stress through enhancing antioxidant capability and regulating hormone-related pathways. Dual-luciferase and electrophoretic mobility shift assays demonstrated that IbbHLH129 binds to the IbYUCCA2 and IbGID1 promoters to activate their expression. These findings suggest that IbbHLH129 enhances cold tolerance in sweetpotato seedlings under short-term cold stress by activating IAA and GA signaling pathways. Our study provides a novel gene resource with promising applications for reducing low-temperature injury to sweetpotato seedlings cultivated in cold growing areas. Full article
(This article belongs to the Special Issue Genetics, Genomics and Evolution of Sweet Potato)
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33 pages, 2031 KB  
Review
Vitamin D Deficiency in Leukemia: Implications for Pathophysiology, Treatment, and Supportive Care
by Zahra Eskandari, Ireneusz Ryszkiel, Amirhossein Faghih Ojaroodi, Haniyeh Bazavar, Shayan Keramat and Agata Stanek
Nutrients 2026, 18(14), 2227; https://doi.org/10.3390/nu18142227 - 9 Jul 2026
Abstract
Leukemia represents a heterogeneous group of hematologic malignancies characterized by the dysregulated proliferation, differentiation, and survival of hematopoietic cells. Vitamin D (VD), a fat-soluble secosteroid hormone, is increasingly recognized not only as a regulator of calcium–phosphate metabolism but also as an important immune–metabolic [...] Read more.
Leukemia represents a heterogeneous group of hematologic malignancies characterized by the dysregulated proliferation, differentiation, and survival of hematopoietic cells. Vitamin D (VD), a fat-soluble secosteroid hormone, is increasingly recognized not only as a regulator of calcium–phosphate metabolism but also as an important immune–metabolic modulator involved in hematopoietic homeostasis, inflammatory signaling, and cellular fate determination. Growing evidence suggests that VD deficiency may influence leukemogenesis, disease progression, treatment responsiveness, and supportive-care outcomes in patients with leukemia. Mechanistic studies indicate that the active metabolite, 1,25-dihydroxyvitamin D3 (calcitriol), modulates leukemic cell biology by activating the vitamin D receptor (VDR) and regulating genomic and non-genomic signaling pathways, including MAPK, PI3K/AKT/mTOR, JAK/STAT, NF-κB, and β-catenin. Through these pathways, VD may affect transcriptional programs governing proliferation, differentiation, apoptosis, autophagy, immune regulation, and treatment resistance. Clinical and observational studies suggest that low 25-hydroxyvitamin D levels may be associated with adverse outcomes in selected leukemia subtypes, including poorer treatment responses, shorter overall survival and relapse-free survival, and shorter time to treatment. However, the available data remain heterogeneous, and causality has not been established. This review provides an integrated translational synthesis of VD deficiency in leukemia, linking molecular mechanisms with subtype-specific clinical evidence and supportive-care implications. Although VD supplementation should not be considered an independent anti-leukemic therapy, individualized assessment and correction of deficiency may represent a rational, low-toxicity component of supportive care. Further prospective and interventional studies are needed to define optimal supplementation strategies, identify responsive patient subgroups, and clarify the clinical relevance of VD status in leukemia. Full article
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14 pages, 6884 KB  
Article
Changes in Ras and Ras-Associated GTPases During Maturation of Porcine Cumulus Cells and Oocytes
by Yuna Nam, Hyeonseo Song, Eunju Seok and Sang-Hee Lee
Animals 2026, 16(14), 2125; https://doi.org/10.3390/ani16142125 - 9 Jul 2026
Abstract
Porcine cumulus–oocyte complexes (COCs) undergo dynamic morphological and molecular changes during maturation; however, cell type- and stage-dependent transcript patterns of Ras-related factors in cumulus cells and oocytes remain unclear. This study investigated changes in Ras-related factors during porcine in vitro maturation (IVM). Porcine [...] Read more.
Porcine cumulus–oocyte complexes (COCs) undergo dynamic morphological and molecular changes during maturation; however, cell type- and stage-dependent transcript patterns of Ras-related factors in cumulus cells and oocytes remain unclear. This study investigated changes in Ras-related factors during porcine in vitro maturation (IVM). Porcine COCs were cultured under IVM conditions supplemented with follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and epidermal growth factor (EGF). Cumulus cells and oocytes were collected at 0, 22, and 44 h of IVM, and cumulus expansion was monitored using time-lapse imaging. Hormone receptor-related factors, CX43, Ras family members, and their RasGAP and RasGEF regulators were analyzed using RT-PCR and qPCR with band-intensity analysis. Progressive cumulus expansion was observed during IVM. In cumulus cells, R-Ras transcript abundance increased at 22 and 44 h, whereas RASA1 transcript abundance was lower at 44 h. In oocytes, R-Ras and H-Ras transcript abundance decreased during maturation. These findings indicate that selected Ras family members and their regulators exhibit distinct cell type- and stage-dependent transcript patterns during porcine COC maturation. These transcript-level findings provide a basis for future protein-level and functional analyses. Full article
(This article belongs to the Special Issue Advances in Pig Reproductive Physiology)
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50 pages, 1344 KB  
Review
Exercise-Induced Hepatic Mitochondrial Reprogramming Across Muscle–Gut–Thyroid Axes in MASLD/MASH
by Jonas M. McCaffrey and Jamal A. Ibdah
Int. J. Mol. Sci. 2026, 27(14), 6112; https://doi.org/10.3390/ijms27146112 - 8 Jul 2026
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing global health burden driven by complex interactions among hepatic lipid accumulation, insulin resistance, chronic inflammation, and mitochondrial dysfunction. Exercise remains the cornerstone of lifestyle therapy for [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing global health burden driven by complex interactions among hepatic lipid accumulation, insulin resistance, chronic inflammation, and mitochondrial dysfunction. Exercise remains the cornerstone of lifestyle therapy for MASLD/MASH; however, its therapeutic benefits extend well beyond weight reduction and involve coordinated molecular adaptations across multiple organ systems. In this review, we introduce hepatic mitochondrial reprogramming as a conceptual framework describing the coordinated remodeling of mitochondrial energetics, quality-control pathways, and redox homeostasis that collectively restore metabolic flexibility and hepatocellular resilience. Exercise activates key metabolic regulators, including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and sirtuin signaling, promoting mitochondrial biogenesis, fatty acid oxidation, oxidative phosphorylation, and mitophagy while suppressing hepatic lipogenesis and oxidative injury. Skeletal muscle-derived myokines, alterations in gut microbial metabolism, and thyroid hormone signaling converge upon hepatic mitochondrial function through complementary endocrine and metabolic pathways. Together, these adaptations reduce hepatic steatosis, lipotoxicity, inflammation, and fibrogenesis while improving insulin sensitivity and metabolic flexibility. Emerging evidence further suggests that exercise-induced mitochondrial remodeling may complement pharmacologic therapies targeting hepatic metabolism, including thyroid hormone receptor-β agonists. Although multi-omics technologies continue to expand our understanding of these adaptive responses, the present review emphasizes the underlying molecular and physiological mechanisms through which exercise remodels hepatic mitochondrial function. We propose that exercise acts as a systems-level mitochondrial remodeling stimulus integrating skeletal muscle-, gut-, and thyroid-derived signals to improve hepatic metabolism and attenuate MASLD/MASH progression. This conceptual framework provides a mechanistic basis for precision exercise prescriptions and future combination therapeutic strategies targeting mitochondrial health. Full article
(This article belongs to the Special Issue Molecular and Physiological Mechanisms of Exercise)
28 pages, 6137 KB  
Article
Integrative Network Pharmacology and Molecular Docking Analysis Reveals the Multitarget Mechanisms of Pterostilbene in Neurodegenerative Diseases
by Natalia Rosiak, Filip Stojceski, Gabriele Maroni, Bartosz Piontek and Judyta Cielecka-Piontek
Pharmaceuticals 2026, 19(7), 1053; https://doi.org/10.3390/ph19071053 - 8 Jul 2026
Abstract
Background: Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), differ in etiology but share several convergent pathological mechanisms. Pterostilbene (PTR) is a natural stilbene with reported antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed [...] Read more.
Background: Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), differ in etiology but share several convergent pathological mechanisms. Pterostilbene (PTR) is a natural stilbene with reported antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed to prioritize putative PTR-associated targets and biological processes potentially relevant to shared neurodegenerative mechanisms. Methods: An integrative in silico workflow combining network pharmacology, protein–protein interaction (PPI) analysis, GO Biological Process (GO BP) enrichment, molecular docking, and molecular dynamics (MD) simulations was applied. GO BP terms were filtered, focused on neurodegeneration- and neuroprotection-related processes, and subjected to REVIGO-based redundancy reduction. Selected targets were further evaluated by docking and 500 ns MD simulations. Results: A total of 181, 165, 128, and 109 shared PTR–disease targets were identified for AD, PD, HD, and ALS, respectively. Redundancy-reduced GO BP analysis indicated associations with neuroinflammation, oxidative stress and reactive oxygen species-related responses, programmed cell death, MAPK/ERK- and PI3K/AKT-related signaling, ion and calcium transport, and lipid-, steroid-, or hormone-associated regulation. PPI topology prioritized SRC, ESR1, and HSP90AA1 as recurrent hub–bottleneck proteins, whereas MD-based structural interpretation focused on ESR1 and HSP90AA1. MD analyses indicated stable PTR interactions with both proteins, with ESR1 showing the most favorable predicted interaction profile. Conclusions: These findings suggest that PTR may interact with shared neurodegeneration-relevant molecular systems, particularly through ESR1- and HSP90AA1-associated mechanisms. However, the results are exclusively computational and should be interpreted as hypothesis-generating, requiring further experimental validation. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 3rd Edition)
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16 pages, 2594 KB  
Article
Conjoint Analysis of Sheep Microbiome, Metabolome, and Transcriptome Revealed the Effect Mechanisms of Feeding with Broccoli Extract
by Gang Zhou, Ying Liu, Xuanxuan Pu, Qiugui Ning, Xiaoshan Guo, Liwei Wang, Yuhong Zhong, Guolian Wang, Xuefeng Guo and Mengzhi Wang
Vet. Sci. 2026, 13(7), 663; https://doi.org/10.3390/vetsci13070663 - 8 Jul 2026
Abstract
Alterations in microbiota, transcript and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16s rRNA, transcriptome sequencing and liquid chromatography–mass spectrometry to investigate intestinal microbiota, genes and metabolic profiles in the ileum of Hu sheep fed [...] Read more.
Alterations in microbiota, transcript and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16s rRNA, transcriptome sequencing and liquid chromatography–mass spectrometry to investigate intestinal microbiota, genes and metabolic profiles in the ileum of Hu sheep fed broccoli extract. Here, we randomly allocated 14 Hu sheep to two diets: a basal diet without any supplementation (NC) and a basal diet supplemented with 200 mg/kg broccoli tail (BT). After 60 days of treatment, blood and jejunal samples were collected for serum biochemical indicators and multi-omics analysis. In this study, the extract of broccoli tails had a significant effect on the serum biochemical indicators, including white blood cells, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean platelet volume, triglycerides and total protein in Hu sheep (p < 0.05). Transcriptomic analysis showed that the 672 differentially expressed genes between the NC and BT groups were primarily enriched in linoleic acid metabolism, steroid hormone biosynthesis, and cholesterol metabolism. Metabolomics analysis using Kyoto Encyclopedia of Genes and Genomes enrichment showed that the 41 differentially abundant metabolites were mainly enriched in bile secretion, vitamin B6 metabolism, and the mTOR signaling pathway. 16S rRNA sequencing results indicated that the extract of broccoli tails increased the relative abundance of Peptostreptococcaceae and decreased the relative abundance of Lachnospiraceae, Lachnospirales, and Bacteroidaceae. Integrated transcriptome, metabolome, and microbiome analysis showed that the gut microbiota and host transcriptomic changes may participate in systemic metabolic regulation by modulating amino acid metabolism, lipid signal transduction, nucleotide metabolism, and vitamin B6-related metabolic pathways. These findings demonstrate that the extract of broccoli tails modulates intestinal gene expression, systemic metabolism, and gut microbial ecology in Hu sheep, providing new insights into the utilization of agricultural byproducts as a functional feed supplement for ruminants. Full article
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