Search Results (1,663)

Drought is one of the major environmental constraints limiting tomato growth and productivity. Identifying regulators that enhance drought tolerance without compromising plant growth is therefore important for tomato production. Homeodomain-leucine zipper (HD-Zip) transcription factors (TFs) play essential roles in plant development and abiotic stress responses; however, the functions of most HD-Zip II members in tomato remain poorly understood. Here, we identified SlHZ07, a drought-responsive HD-Zip II TF, through transcriptome analysis and characterized its biological function in tomato. SlHZ07 was rapidly induced by drought stress and localized predominantly to the nucleus. Overexpression of SlHZ07 significantly enhanced drought tolerance, whereas RNAi-mediated suppression increased drought sensitivity. Physiological analyses showed that SlHZ07 overexpression reduced reactive oxygen species (ROS) accumulation, enhanced antioxidant enzyme activities, upregulated expression of ROS-scavenging genes, and alleviated membrane damage under drought stress. Hormone analyses revealed that SlHZ07 positively regulated jasmonic acid (JA) accumulation and the expression of JA biosynthetic genes, including OPR2, OPR3, JAR1, and AOC, but did not alter endogenous abscisic acid (ABA) levels under well-watered conditions. Furthermore, SlHZ07 promoted vegetative growth by increasing endogenous gibberellin (GA) levels and upregulating the expression of the GA biosynthetic genes GA20ox2 and GA20ox4. Together, our findings identify SlHZ07 as a previously uncharacterized positive regulator that coordinates plant growth and drought adaptation by integrating GA biosynthesis, JA homeostasis, and ROS detoxification. These results expand our understanding of HD-Zip II TFs and provide a promising genetic target for improving drought tolerance in tomato. Full article

Thyroid hormone (TH, the active metabolite T₃)) plays a critical role in neuronal proliferation and differentiation during development. However, its role in adult neurogenesis (ANG) remains incompletely understood. To gain insight into the role of T3 in ANG, we used a mouse model (Dio3KO mouse) with a deficiency in type 3 deiodinase, which clears T3 in the brain. We observed that the number of DCX/RBFOX3 double-positive cells is significantly reduced in the subgranular zone (SGZ) and the subventricular zone (SVZ) of 10-month-old female Dio3KO mice, suggesting impaired ANG in these neurogenic niches. However, no significant changes were observed in IBA1/GFAP or OLIG2/GFAP double-positive cells, suggesting that the neurogenic deficits are not associated with neuroinflammation, gliosis, or altered oligodendrogenesis. Cortical RNA-seq analysis further identified dysregulated T3-responsive genes implicated in ANG, revealing marked sex-dependent differences in gene expression. Proof-of-concept experiments in type 2 deiodinase 2 (Dio2) and Dio3 double knockout mice revealed a rescue of the neurogenic phenotype, supporting the hypothesis that loss of DIO2-mediated T3 generation counteracts the detrimental effects of DIO3 deficiency on ANG. Collectively, these findings identify DIO3- and DIO2-me fotmdiated T3 homeostasis in neural cells as critical contributors to T3-dependent ANG in females, with implications for neurodegenerative diseases and their sexually dimorphic prevalence. Full article

Papaya is a trioecious species, but a unified framework for comparing floral sex differentiation has been lacking. We combined stereomicroscopy, paraffin sectioning, and scanning electron microscopy to establish a continuous 12-stage developmental system from floral primordium initiation to anthesis. Male, female, and hermaphroditic flowers followed a common developmental trajectory during Stages 1–4 and diverged at Stage 5. Male flowers formed fertile stamens and a reduced pistillode, female flowers developed a complete gynoecium without stamens, and hermaphroditic flowers displayed normal, aborted, or transitional pistils and carpellodic stamens. RNA sequencing and weighted gene co-expression network analysis of morphologically defined tissues identified gene modules associated with normal pistil development, distinct modes of pistil abortion, and stamen carpellody. These modules were enriched in chromatin and RNA regulation, protein homeostasis, floral-organ identity, hormone and receptor-kinase signaling, pollen-wall formation, and stress-responsive pathways, yielding 30 representative candidate genes. This developmental framework integrates developmental morphology with transcriptional programs underlying reproductive-organ fate and plasticity in papaya. Full article

AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that integrates energetic, nutrient, hormonal, redox, and stress signals to coordinate cellular and whole-body energy homeostasis. Although AMPK was initially characterized primarily as a sensor of changes in cellular AMP/ATP ratios, recent studies have revealed additional layers of regulation involving upstream kinases, post-translational modifications, heterotrimeric isoform composition, subcellular compartmentalization, and tissue-specific signaling. In this review, we provide an updated overview of the molecular mechanisms regulating AMPK activity, its major downstream metabolic and homeostatic pathways, its roles in metabolic, cardiovascular, neurodegenerative, muscular, malignant, and age-associated diseases, and current strategies for pharmacological AMPK modulation. We compare indirect activators, including metformin and naturally derived compounds, with direct small-molecule agonists targeting the allosteric drug and metabolite (ADaM) site, and emerging activators that selectively engage specific AMPK isoforms, tissues, or subcellular pools. We also discuss endogenous AMPK regulators, including microbiota-derived metabolites, and critically evaluate the potential adverse consequences of sustained or systemic AMPK activation. Collectively, current evidence indicates that the therapeutic effects of AMPK activation are highly dependent on tissue, heterotrimer composition, subcellular localization, disease stage, and the magnitude and duration of activation. Rather than indiscriminate systemic activation, future AMPK-directed therapies are therefore likely to benefit from isoform-, tissue-, and compartment-selective approaches that preferentially engage disease-relevant AMPK signaling while minimizing off-target effects. Continued characterization of AMPK signaling specificity and the development of selective pharmacological modulators should facilitate the translation of AMPK biology into more precise therapies for metabolic and other chronic diseases. Full article

Leaf-color mutants are crucial for elucidating chlorophyll metabolism mechanisms. Here, we identified yel, a stably inherited rice mutant with a dwarf and yellow-green leaf phenotype controlled by a single recessive nuclear gene. Using BSA-seq, we mapped the candidate causal gene to OsMPEC, encoding a magnesium protoporphyrin IX monomethyl ester cyclase with a G→T substitution. Multi-omics analysis revealed that the functional deficiency of OsMPEC protein—despite unchanged transcript levels—triggers global transcriptional repression of the chlorophyll metabolic network. This defect caused distinct metabolic consequences: impaired synthesis at the early stage (yel1) and toxic metabolite accumulation at the later stage (yel2). Furthermore, metabolic collapse induced systemic reprogramming of hormone signaling, shifting from pro-growth to stress and senescence modes. We propose that the yel phenotype is associated with a self-reinforcing inhibitory loop of “passive synthesis inhibition” and “active degradation acceleration.” This study clarifies OsMPEC’s role in chlorophyll homeostasis and demonstrates how a single genetic defect drives phenotype- through to network-level cascading effects. Full article

Background/Objectives: Skin aging involves interconnected inflammatory, oxidative, hormonal, extracellular matrix (ECM), and cellular senescence-related mechanisms, supporting the need for multitarget approaches. This study aimed to evaluate the effects of a multicomponent natural product-based injectable formulation developed in Korean medicine practice, Dong-An Pharmacopuncture (DAP), on skin aging-related pathways. Methods: A network pharmacology approach was used to identify the active compounds, predicted molecular targets, and signaling pathways associated with DAP. Sixty-two active compounds from 11 constituent materials were screened, and 70 final targets were identified using STITCH-based prediction, intersection with GeneCards-derived skin aging-related targets, and quality filtering. Results: Herb-compound-target network analysis yielded 225 compound–target interactions across 292 edges. Protein-protein interaction analysis identified a highly connected network with 1,334 edges, and hub analysis converged on 10 core targets: TNF, IL6, ESR1, TP53, AKT1, PPARG, EGFR, PTGS2, CASP3, and PPARA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses identified four major mechanistic axes: inflammatory and oxidative stress regulation, hormonal skin homeostasis, tissue repair and ECM remodeling, and cellular senescence-related regulation. Because DAP is administered by injection, a Good Laboratory Practice-compliant single-dose subcutaneous toxicity study was additionally conducted in Sprague–Dawley rats, which showed no mortality, abnormal clinical signs, or histopathological findings attributable to DAP at 1.0 mL/head. Conclusions: The findings in this study provide a systems-level framework for the predicted multitarget mechanisms of DAP in skin aging-related pathways and support the need for further experimental validation of its predicted mechanisms and repeated-dose safety. Full article

Background: Physical exercise induces coordinated endocrine and metabolic adaptations that contribute to the regulation of glucose homeostasis, lipid metabolism, stress responses, and anabolic processes. However, the integrated effects of combined aerobic and resistance exercise on multiple endocrine and metabolic outcomes require further investigation. This study aimed to evaluate the effects of a 12-week combined aerobic and resistance exercise program on endocrine and metabolic parameters in normal-weight and mildly overweight adults. Methods: A total of 60 adults were randomly allocated to an exercise group (EX, n = 30) or a control group (CON, n = 30). The EX-group completed a supervised 12-week combined exercise program consisting of three 60 min sessions per week, including aerobic exercise and multi-joint resistance training, whereas the CON-group maintained their habitual physical activity levels. Endocrine parameters, including insulin, glucagon, cortisol, growth hormone (GH), thyroid hormones, and sex-specific hormones, as well as fasting glucose, lipid profile, and homeostasis model assessment of insulin resistance (HOMA-IR), were assessed at baseline and after 12 weeks. Results: Compared with the control condition, the exercise program was associated with favorable changes in endocrine and metabolic profiles. The EX-group showed reductions in fasting insulin, cortisol, fasting glucose, and HOMA-IR, together with increased GH levels. Favorable changes were also observed in the lipid profile, including reductions in total cholesterol, low-density lipoprotein cholesterol (LDL), and triglycerides and an increase in high-density lipoproteins cholesterol (HDL). In the male subgroup, total testosterone increased following the intervention, whereas estradiol changes in the female subgroup were more limited. Changes in insulin were associated with changes in glucose regulation and lipid parameters, while GH and cortisol changes showed additional associations with metabolic outcomes. Conclusions: These findings support the role of structured combined exercise as a non-pharmacological strategy for promoting endocrine and metabolic health and preventing metabolic dysfunction. Full article

Soybean (Glycine max (L.) Merr.) was originally domesticated in China and is a kind of significant leguminous crop, which can fix atmospheric nitrogen to bioavailable nitrogen in association with rhizobia. Ceramides, intermediates of sphingolipids, are crucial structural components in membrane formation and also function as signaling molecules, which play crucial roles in plant development and defense. Although Arabidopsis ceramide synthase genes AtLOH1 and AtLOH3 overexpression plants increased biomass compared to the wild type, the potential mechanism in plant growth was still unclear. A soybean ceramide synthase gene 1 (GmCS1) has a high expression level in the stem, and the protein is localized in the endoplasmic reticulum. Overexpression of GmCS1 promotes soybean lateral branch development for effective branch formation, significantly increasing the number of lateral branches and pods. Using transcriptomic profiles, we found that GmCS1 overexpression lines displayed the upregulation of plant hormone signal transduction pathway gene expression in developmental branches. Actually, Indole-3-acetic acid (IAA) induces bud outgrowth rather than initiation according to the determination of endogenous IAA and cytokinin (CKs) in soybean lateral branches. Collectively, these results suggest that GmCS1 may be a functional ceramide synthase gene in soybean, with the GmCS1-mediated regulatory network playing a crucial role in controlling branch development by IAA and CKs homeostasis. Exploring the regulation mechanisms by GmCS1 overexpression lines is essential for Ideal Soybean Architecture (ISA) innovation. Full article

Climate change is increasing the frequency and severity of abiotic stresses, including drought, salinity, waterlogging, and temperature extremes, thereby threatening the productivity and quality of Brassica crops. This review synthesizes recent progress in abiotic stress tolerance from physiological, genetic, epigenetic, and multi-omics perspectives, with an emphasis on how mechanistic discoveries can be translated into breeding decisions. We first outline the signaling hierarchy that links stress perception at the plasma membrane and cell wall interface to Ca²⁺ signaling, MAPK cascades, hormone crosstalk, osmotic adjustment, ROS homeostasis, and metabolic reprogramming. We then examine the genetic architecture of stress tolerance through QTL mapping, GWAS, and functional genomics, highlighting how allopolyploidy, subgenome specialization, homoeologous gene divergence, and alternative splicing create both opportunities and complications for Brassica improvement. We further evaluate how transcriptomic, epigenomic, metabolomic, and microbiome-related data are revealing regulatory complexity but remain underused for prediction and causal inference. Major bottlenecks include the inefficient conversion of association signals into validated functional markers, the descriptive rather than predictive use of multi-omics datasets, limited mechanistic understanding of combined stresses, and insufficient field validation across genetic backgrounds. Finally, we discuss integrated breeding strategies, including marker-assisted selection, genomic selection, genome editing, wild germplasm utilization, microbiome-assisted approaches, and synthetic biology. By connecting stress biology with translational breeding, this review provides a framework for developing climate-resilient Brassica cultivars. Full article

Hair follicle homeostasis is influenced by hormonal pathways, the scalp microenvironment, and environmental stressors such as pollution, UV radiation, and oxidative stress. Elissara^®, a polyphenol-enriched botanical ingredient, has shown benefits for scalp moisturization, barrier function, sebum regulation, and redness. Building on these scalp-level benefits, we investigated Elissara’s effects on follicular signaling, survival-associated biomarkers, oxidative damage, and androgen-related pathways as potential contributors to follicular health, using in silico, in vitro, and ex vivo models. Molecular docking (AutoDock Vina) of the main Elissara bioactives (oleuropein, hydroxytyrosol, verbascoside, carnosic acid, carnosol, and quercetin) identified SRD5A2 as a favorable predicted target, with individual binding energies ranging from −8.70 to −9.73 kcal/mol, approaching finasteride/dutasteride reference values. As an exploratory approach, simultaneous multi-ligand docking showed favorable global docking outputs for several targets, indicating that multiple bioactives could be structurally accommodated within complementary regions of the binding site. In human follicle dermal papilla cells, Elissara significantly increased BrdU incorporation to 245.70% of control at 0.002% and reduced SRD5A2 protein levels by 18.48% at 0.006%. In human scalp explants, Elissara at 200 µg/mL increased β-catenin, Bcl-2, and collagen IV under basal conditions and counteracted acute PM_2.5/UVA-induced alterations in β-catenin, Ki67-positive cells, Bcl-2, IGF-1, collagen IV, and protein carbonylation. Together, these findings support the potential of Elissara as a promising nutricosmetic ingredient for supporting follicular resilience through multiple follicle-relevant pathways. Clinical studies assessing hair growth outcomes are needed to determine whether these preclinical findings translate into measurable benefits. Full article

Background and Objectives: Endometriosis is associated with chronic inflammation, immune dysregulation, oestrogen-dependent growth, oxidative stress, altered steroid hormone metabolism, compromised epithelial barrier integrity, and the production of bioactive microbial metabolites. These interconnected alterations have been proposed to create, in principle, a permissive local microenvironment for malignant transformation. This narrative review examines whether endometriosis-associated dysregulation of the gut and reproductive tract microbiota may act as a hypothetical biological modulator linking these multi-axis changes to endometrial carcinogenesis, with attention to immunological, endocrine, metabolic, microbial–metabolite, oxidative, and barrier-related pathways. Material and Methods: We narratively integrated current evidence on gut and reproductive tract microbiota alterations relevant to endometrial homeostasis, with emphasis on the estrobolome, low-biomass uterine microbial communities, inflammatory and immune signaling, microbial metabolites, and pathways implicated in carcinogenesis. Results: Available data suggest that dysbiosis may influence endometrial carcinogenesis through interconnected endocrine, inflammatory, metabolic, and immune mechanisms. Attention has been given to loss of Lactobacillus dominance, enrichment of anaerobic and pro-inflammatory taxa, altered estrogen recirculation, progesterone resistance, Toll-like receptor activation, NF-κB/STAT3 signaling, COX-2/PGE2 activity, PI3K/AKT/mTOR pathway activation, oxidative stress, macrophage polarization, and impaired natural killer cell surveillance. These alterations may contribute to a permissive microenvironment characterized by persistent inflammation, defective immune control, and disrupted endometrial homeostasis. However, the current literature remains limited by small and heterogeneous cohorts, predominantly cross-sectional designs, contamination risk, and marked methodological variability, particularly in low-biomass uterine samples. Conclusions: Current evidence supports the view that microbiome dysregulation is a context-dependent biological modulator that intersects with endocrine, inflammatory, metabolic, immune, oxidative, and barrier-related pathways relevant to endometrial carcinogenesis. Microbiome dysbiosis should be regarded as a hypothetical contributory factor rather than as an established causal driver. Its near-term translational relevance appears greater for biomarker development and risk stratification than for immediate microbiome-directed therapy. Longitudinal, standardized, and functionally integrated studies are needed to clarify whether microbiome-associated signatures can be translated into clinically meaningful prevention and management strategies in endometrial cancer. Full article

Rare earth elements (REEs) are increasingly recognized as modulators of male reproductive health. This review presents the first comprehensive and critical analysis of the detrimental and potentially beneficial effects of REEs on male vertebrate reproductive function. In vivo and in vitro studies show that elements, particularly Gadolinium, Lanthanum, and Yttrium, share a toxicological profile characterized by oxidative stress, inflammation, mitochondrial dysfunction, endocrine disruption, and impairment of the blood–testis barrier. These mechanisms converge on both somatic and germ cell populations, ultimately compromising spermatogenesis and hormonal balance. Limited epidemiological data in humans are consistent with experimental findings, indicating inverse associations between seminal REE levels and sperm quality. CeO₂ nanoparticles represent an exception, showing dose-dependent duality: although some murine studies describe toxic effects, a broader and more consistent body of evidence indicates their protective action by restoring testicular homeostasis in diabetic models, in rats exposed to pesticides, pharmacological agents or irradiation, and in in vitro-treated spermatozoa. Preliminary data on Yttrium (YO) and Gadolinium (GdVO₄) nanoparticles similarly point to protective effects under pathological conditions, whereas Neodymium and Samarium show reproductive toxicity, including hormonal disruption and impaired sperm quality. Overall, REEs cannot be considered a homogeneous class: some pose reproductive hazards, others show potential biomedical utility. A systematic, mechanistic research framework is needed to resolve these dualities. It should contextualise reproductive risks in relation to the growing environmental and occupational exposure to REEs, while simultaneously exploring the biomedical potential of those elements that exhibit protective profiles. Full article

Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age and is characterized by ovarian hyperandrogenism and irregular ovulation. This often leads to infertility. Beyond reproduction, PCOS causes widespread metabolic issues such as insulin resistance (IR), increasing long-term risks for diabetes, obesity, and heart disease. In a vicious cycle, IR acts as a core driver of both clinical symptoms and associated obesity, whereas compensatory hyperinsulinemia stimulates ovarian androgen production, causing ovulatory dysfunction and worsening weight gain, with immune imbalances exacerbating systemic chronic low-grade inflammation (CLGI). Berberine is a natural plant alkaloid that, owing to its multifaceted metabolic effects—including activation of 5′ adenosine monophosphate (AMP)-activated protein kinase (AMPK) and improvement of insulin sensitivity—effectively supports the restoration of homeostasis in women with PCOS. The aim of this narrative review is to comprehensively analyze the metabolic and anti-inflammatory actions of berberine, which, in combination with the known pathomechanisms of PCOS, may constitute a rationale for its therapeutic application. Attention was given to the necessity of actions aimed at increasing the bioavailability of berberine and to the consequences of the fact that berberine, unlike metformin, which is commonly used and has similar properties, is a dietary supplement and not a Food and Drug Administration (FDA)-approved prescription drug. Full article

Objectives: This study clarified sex-specific short- and long-term impacts of maternal excessive palm oil (plant-derived saturated) and lard (animal-derived saturated fat) intake on offspring reproductive health and underlying mechanisms. Methods: Female mice were randomized to control, palm oil, or lard diets during gestation and lactation. Offspring received a control diet post-weaning until adulthood, followed by an optional 16-week HFD rechallenge. Gonadal weight and organ index, sperm quality, ovarian follicle number, serum sex hormones, metabolic phenotypes (serum lipid profiles, glucose and insulin tolerance), oxidative stress, apoptosis, proliferation, and transcriptomic profiles were detected at weaning, early and late adulthood. Results: In males, excessive maternal lard intake significantly induces sperm malformation and reduces seminiferous tubule diameter and spermatogenic epithelium thickness upon HFD rechallenge during adulthood, with no changes in oxidative stress, proliferation, and apoptosis. Transcriptomics identified Slc24a5 upregulation as a potential correlate through metal ion transmembrane transporter activity and cellular calcium ion homeostasis. Under normal adult diets, reduced sperm motility resulting from maternal excess lard may be mediated by apoptosis, whereas that induced by maternal high palm oil likely arises from suppressed proliferation and thinner spermatogenic epithelium. GO analysis revealed palm oil-specific Ugt1a5 upregulation associated with altered steroid hormone metabolism. In females, maternal palm oil intake reduced primordial follicles and increased atresia, with sequencing predicted to involve Nedd4 downregulation; lard intake elevated ovarian oxidative stress and atresia only upon HFD rechallenge, with Lamc3 upregulation predicted as a putative regulatory factor. Conclusions: Maternal excessive intake of saturated fat exerts offspring reproductive damage in a sex-specific and source-dependent manner with distinct mechanisms. This work provides novel insights into fat source-dependent and sex-specific effects of nutritional interventions during pregnancy and lactation. Full article

Gonadotropin-releasing hormone agonists are used to treat central precocious puberty and are increasingly prescribed in gender-affirming care. Despite well-established reproductive effects, their broader physiological effects during puberty remain poorly understood. Male and female Wistar rats received a depot triptorelin injection at pubertal onset. Body mass, food intake, and locomotor activity were monitored. After 28 days, reproductive function was assessed, and pituitary and hypothalamic gene expression was analyzed. Changes in gonadal weight, estrous cycle, folliculogenesis, seminiferous tubules’ morphology, and sperm count confirmed the suppression of pubertal maturation. Triptorelin downregulated Gnrhr and Lhb, demonstrating suppression of gonadotrope function. Despite comparable reproductive suppression, metabolic responses to triptorelin were strongly sex-dependent. Females exhibited increased body weight gain accompanied by delayed hyperphagia, whereas males showed reduced body weight gain, unchanged food intake, and increased mean locomotor speed. Female-specific transcriptional remodeling was observed in the hypothalamus, characterized by downregulation of Npy and Lepr and upregulation of Sst and Kiss1 expression. Collectively, these findings demonstrate that pubertal triptorelin treatment induces profound reproductive suppression in both sexes while eliciting sex-specific hypothalamic adaptations in pathways regulating energy homeostasis. This suggests that puberty blockers exert broader neuroendocrine effects beyond the suppression of reproductive maturation. Full article