Search Results (2,407)

The purpose of this article is to examine a previously unrecognized role for the vasopressin–oxytocin (VP-OT) system in mammalian “stress-response hormesis.” The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, is introduced here to contextualize the dynamic roles of oxytocin and vasopressin. As with hormesis, the properties of the VP-OT system are context-, time-, and dose-sensitive. Here we suggest that one key to understanding hormesis is the fact that VP and OT and their receptors function as an integrated system. The VP-OT system is capable of changing and adapting to challenges over time, including challenges necessary for survival, reproduction and sociality. Prior research suggests that many beneficial effects of OT are most apparent only following stressful experiences, possibly reflecting interactions with VP, its receptors and other components of the hypothalamic–pituitary–adrenal axis. The release of OT is documented following various kinds of hormetic experiences such as birth, vigorous exercise, ischemic events and the ingestion of emetics, including psychedelics. The phasic or cyclic modulation of VP and related “stress” hormones, accompanied or followed by the release of OT, creates conditions that conform to the core principles of hormesis. This concept is reviewed here in the context of other hormones including corticotropin releasing hormone (CRH) and urocortin, as well as cytokines. In general, VP and classic “stress hormones” support an active response, helping to quickly mobilize body systems. OT interacts with all of these, and may subsequently re-establish homeostasis and precondition the organism to deal with future stressors. However, the individual history of an organism, including epigenetic modifications of classical stress hormones such as VP, can moderate the effects of OT. Oxytocin’s effects also help to explain the important role of sociality in mammalian resilience and longevity. A hormetic perspective, focusing on a dynamic VP-OT system, offers new insights into emotional and physical disorders, especially those associated with the management of chronic stress, and helps us to understand the healing power of social behavior and perceived safety. Full article

Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article

One of the important traits of many plant growth-promoting rhizobacteria (PGPR) is the biocontrol of phytopathogens. Some PGPR metabolize phytohormone abscisic acid (ABA); however, the role of this trait in plant–microbe interactions is scarcely understood. Phytopathogenic fungi produce ABA and use this property as a negative regulator of plant resistance. Therefore, interactions between ABA-producing necrotrophic phytopathogen Botrytis sp. BA3 with ABA-metabolizing rhizobacterium Rhodococcus sp. P1Y were studied in a batch culture and in gnotobiotic hydroponics with sunflower seedlings. Rhizobacterium P1Y possessed no antifungal activity against BA3 and metabolized ABA, which was synthesized by BA3 in vitro and in associations with sunflower plants infected with this fungus. Inoculation with BA3 and the application of exogenous ABA increased the root ABA concentration and inhibited root and shoot growth, suggesting the involvement of this phytohormone in the pathogenesis process. Strain P1Y eliminated negative effects of BA3 and exogenous ABA on root ABA concentration and plant growth. Both microorganisms significantly modulated the hormonal status of plants, affecting indole-3-acetic, salicylic, jasmonic and gibberellic acids, as well as cytokinins concentrations in sunflower roots and/or shoots. The hormonal effects were complex and could be due to the production of phytohormones by microorganisms, changes in ABA concentrations and multiple levels of crosstalk in hormone networks regulating plant defense. The results suggest the counteraction of rhizobacteria to ABA-producing phytopathogenic fungi through the metabolism of fungal ABA. This expands our understanding of the mechanisms related to the biocontrol of phytopathogens by PGPR. Full article

Beyond its crucial role as a tight barrier to protect the nervous system, the Blood–Brain Barrier (BBB) is increasingly being recognized for its physiological processes that affect brain function and behavior. In Drosophila melanogaster, the BBB expresses sex-specific transcripts, and a change in the sexual identity of adult BBB cells results in a significant reduction in male courtship behavior. The molecular nature of this BBB/brain interaction and the molecules that mediate it are unknown. Here we feminize BBB cells by targeted expression of the Drosophila female-specific master regulator TraF in otherwise normal males. We examined the effect on RNA expression in dissected brains by RNA sequenc-ing. We find that 283 transcripts change in comparison to normal control males. Tran-scripts representing cell signaling processes and synaptic communication are enriched, as are hormonal mediators. These transcripts provide a valuable resource for addressing questions about BBB and brain interaction. Full article

Early blight, caused by the pathogen Alternaria solani, is a major fungal disease impacting potato production globally, with reported yield losses of up to 40% in susceptible varieties. As one of the most common diseases affecting potatoes, its incidence has been steadily increasing year after year. This study aimed to elucidate the molecular mechanisms underlying resistance to early blight by comparing gene expression profiles in resistant (B1) and susceptible (D30) potato seedlings. Transcriptome sequencing was conducted at three time points post-infection (3, 7, and 10 dpi) to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and pathway enrichment analyses were performed to explore resistance-associated pathways and hub genes. Over 11,537 DEGs were identified, with the highest number observed at 10 dpi. Genes such as LOC102603761 and LOC102573998 were significantly differentially expressed across multiple comparisons. In the resistant B1 variety, upregulated genes were enriched in plant–pathogen interaction, MAPK signaling, hormonal signaling, and secondary metabolite biosynthesis pathways, particularly flavonoid biosynthesis, which likely contributes to biochemical defense against A. solani. WGCNA identified 24 distinct modules, with hub transcription factors (e.g., WRKY33, MYB, and NAC) as key regulators of resistance. These findings highlight critical molecular pathways and candidate genes involved in early blight resistance, providing a foundation for further functional studies and breeding strategies to enhance potato resilience. Full article

Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, is widely found in various consumer products and poses significant health risks, particularly through hormone receptor interactions, oxidative stress, and mitochondrial dysfunction. BPA exposure is associated with reproductive, metabolic, and neurodevelopmental disorders. Melatonin, a neurohormone with strong antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic agent to counteract the toxic effects of BPA. This review consolidates recent findings from in vitro and animal/preclinical studies, highlighting melatonin’s protective mechanisms against BPA-induced toxicity. These include its capacity to reduce oxidative stress, restore mitochondrial function, modulate inflammatory responses, and protect against DNA damage. In animal models, melatonin also mitigates reproductive toxicity, enhances fertility parameters, and reduces histopathological damage. Melatonin’s ability to regulate endoplasmic reticulum (ER) stress and cell death pathways underscores its multifaceted protective role. Despite promising preclinical results, human clinical trials are needed to validate these findings and establish optimal dosages, treatment durations, and safety profiles. This review discusses the wide range of potential uses of melatonin for treating BPA toxicity and suggests directions for future research. Full article

This study aimed to evaluate and optimize the effects of three auxin types—indole-3-butyric acid (IBA), naphthaleneacetic acid (NAA), and indole-3-acetic acid (IAA)—applied at four concentrations (1000, 3000, 5000, and 8000 ppm) on the rooting performance of Photinia × fraseri Dress. stem cuttings. The experiment was conducted under controlled greenhouse conditions using a sterile perlite medium. Rooting trays were placed on bottom-heated propagation benches maintained at a set temperature of 25 ± 2 °C to stimulate root formation. However, the actual rooting medium temperature—measured manually every four days from the perlite zone using a calibrated thermometer—ranged between 18 °C and 22 °C, with an overall average of approximately 20 ± 2 °C. The average values of these root-zone temperatures were used in the statistical analyses. Rooting percentage, root number, root length, callus formation, and mortality rate were recorded after 120 days. In addition to classical one-way ANOVA, response surface methodology (RSM) was employed to model and optimize the interactions between auxin type, concentration, and temperature. The results revealed that 5000 ppm IBA significantly enhanced rooting performance, yielding the highest rooting percentage (85%), average root number (5.80), and root length (6.30 cm). RSM-based regression models demonstrated strong predictive power, with the model for rooting percentage explaining up to 92.79% of the total variance. Temperature and auxin concentration were identified as the most influential linear factors, while second-order and interaction terms—particularly T·ppm—contributed substantially to root length variation. These findings validate IBA as the most effective exogenous auxin for the vegetative propagation of Photinia × fraseri Dress. and provide practical recommendations for optimizing hormone treatments. Moreover, the study offers a robust statistical modeling framework that can be applied to similar propagation systems in woody ornamental plants. Full article

Background: Against the backdrop of the large-scale and intensive development of the livestock industry, enhancing the reproductive efficiency of cattle has become a crucial factor in industrial development. Holstein cows, as the most predominant dairy cattle breed globally, are characterized by high milk yield and excellent milk quality. However, their reproductive efficiency is comprehensively influenced by a variety of complex factors, and improving their reproductive performance faces numerous challenges. The ovary, as the core organ of the female reproductive system, plays a decisive role in embryonic development and pregnancy maintenance. It is not only the site where eggs are produced and developed but it also regulates the cow’s estrous cycle, ovulation process, and the establishment and maintenance of pregnancy by secreting various hormones. The normal functioning of the ovary is crucial for the smooth development of the embryo and the successful maintenance of pregnancy. Methods: Currently, traditional sequencing technologies have obvious limitations in deciphering ovarian function and reproductive regulatory mechanisms. To overcome the bottlenecks of traditional sequencing technologies, this study selected Holstein cows as the research subjects. Ovarian samples were collected from one pregnant and one non-pregnant Holstein cow, and single-nucleus transcriptome sequencing technology was used to conduct an in-depth study on the ovarian cells of Holstein cows. Results: By constructing a cell type-specific molecular atlas of the ovaries, nine different cell types were successfully identified. This study compared the proportions of ovarian cell types under different physiological states and found that the proportion of endothelial cells decreased during pregnancy, while the proportions of granulosa cells and luteal cells increased significantly. In terms of functional enrichment analysis, oocytes during both pregnancy and non-pregnancy play roles in the “cell cycle” and “homologous recombination” pathways. However, non-pregnant oocytes are also involved in the “progesterone-mediated oocyte maturation” pathway. Luteal cells during pregnancy mainly function in the “cortisol synthesis and secretion” and “ovarian steroidogenesis” pathways; non-pregnant luteal cells are mainly enriched in pathway processes such as the “AMPK signaling pathway”, “pyrimidine metabolism”, and “nucleotide metabolism”. Cell communication analysis reveals that there are 51 signaling pathways involved in the pregnant ovary, with endothelial cells, granulosa cells, and luteal cells serving as the core communication hubs. In the non-pregnant ovary, there are 48 pathways, and the interaction between endothelial cells and stromal cells is the dominant mode. Conclusions: This study provides new insights into the regulatory mechanisms of reproductive efficiency in Holstein cows. The differences in the proportions of ovarian cell types, functional pathways, and cell communication patterns under different physiological states, especially the increase in the proportions of granulosa cells and luteal cells during pregnancy and the specificity of related functional pathways, indicate that these cells play a crucial role in the reproductive process of cows. These findings also highlight the importance of ovarian cells in pathways such as “cell cycle”, “homologous recombination”, and “progesterone-mediated oocyte maturation”, as well as the cell communication mechanisms in regulating ovarian function and reproductive performance. Full article

The enteroendocrine system of the gastrointestinal (GI) tract is the largest endocrine organ in the human body, playing a central role in the regulation of hunger, satiety, digestion, and energy homeostasis. Numerous factors—including dietary components, physical activity, and the gut microbiota—affect the secretion of GI hormones. This study aims to analyze how these factors modulate enteroendocrine function and influence systemic metabolic regulation. This review synthesizes the current scientific literature on the physiology and distribution of enteroendocrine cells and mechanisms of hormone secretion in response to macronutrients, physical activity, and microbial metabolites. Special attention is given to the interactions between gut-derived signals and central nervous system pathways involved in appetite control. Different GI hormones are secreted in specific regions of the digestive tract in response to meal composition and timing. Macronutrients, particularly during absorption, stimulate hormone release, while physical activity influences hormone concentrations, decreasing ghrelin and increasing GLP-1, PYY, and leptin levels. The gut microbiota, through fermentation and metabolite production (e.g., SCFAs and bile acids), modulates enteroendocrine activity. Species such as Akkermansia muciniphila are associated with improved gut barrier integrity and enhanced GLP-1 secretion. These combined effects contribute to appetite regulation and energy balance. Diet composition, physical activity, and gut microbiota are key modulators of gastrointestinal hormone secretion. Their interplay significantly affects appetite regulation and metabolic health. A better understanding of these relationships may support the development of personalized strategies for managing obesity and related disorders. Full article

Hormone-dependent breast cancer, particularly in its treatment-resistant forms, remains a significant therapeutic challenge. In this study, we applied a fully computational strategy to design steroid-based compounds capable of simultaneously targeting three key receptors involved in disease progression: progesterone receptor (PR), estrogen receptor alpha (ER-α), and HER2. Using a robust 3D-QSAR model (R² = 0.86; Q²_LOO = 0.86) built from 52 steroidal structures, we identified molecular features associated with high anticancer potential, specifically increased polarizability and reduced electronegativity. From a virtual library of 271 DFT-optimized analogs, 31 compounds were selected based on predicted potency (pIC₅₀ > 7.0) and screened via molecular docking against PR (PDB 2W8Y), HER2 (PDB 7JXH), and ER-α (PDB 6VJD). Seven candidates showed strong binding affinities (ΔG ≤ −9 kcal/mol for at least two targets), with Estero-255 emerging as the most promising. This compound demonstrated excellent conformational stability, a robust hydrogen-bonding network, and consistent multitarget engagement. Molecular dynamics simulations over 100 nanoseconds confirmed the structural integrity of the top ligands, with low RMSD values, compact radii of gyration, and stable binding energy profiles. Key interactions included hydrophobic contacts, π–π stacking, halogen–π interactions, and classical hydrogen bonds with conserved residues across all three targets. These findings highlight Estero-255, alongside Estero-261 and Estero-264, as strong multitarget candidates for further development. By potentially disrupting the PI3K/AKT/mTOR signaling pathway, these compounds offer a promising strategy for overcoming resistance in hormone-driven breast cancer. Experimental validation, including cytotoxicity assays and ADME/Tox profiling, is recommended to confirm their therapeutic potential. Full article

Aggressiveness in dogs is a complex behavioral trait with implications for animal welfare and public safety. Despite domestication, dogs retain aggressive tendencies shaped by both genetic and environmental factors. This systematic review synthesizes the literature from 2000 to 2024 on the genetic and environmental bases of canine aggression. Using PRISMA 2020 guidelines, 144 articles were retrieved from Scopus and PubMed and screened in two phases, resulting in 33 studies selected for analysis. These were evaluated using a 20-question grid across seven categories, including phenotyping, genetic analysis, population structure, and future directions. The studies support a polygenic model of aggressiveness, with associations reported for genes involved in neurotransmission, hormone signaling, and brain function. However, inconsistencies in phenotyping, small sample sizes, and a limited consideration of environmental factors hinder robust conclusions. Most studies focused on popular companion breeds, while those commonly labeled as aggressive were underrepresented. The findings highlight the relevance of gene–environment interactions but underscore that aggression is often poorly defined and measured across studies. Future research should prioritize standardized phenotyping tools, broader breed inclusion, and the functional validation of genetic findings. These efforts will improve the understanding of dog aggression and inform breeding, behavioral assessment, and public policy. Full article

Thyroid hormones play a crucial role in regulating metabolism and cardiovascular function, with even mild dysfunction—such as subclinical hypothyroidism—negatively impacting heart health. While previous studies have confirmed the effects of iodine, selenium, and vitamin D on thyroid regulation and inflammation, the combined role of these nutrients in reducing cardiovascular disease (CVD) risk in autoimmune thyroid disorders remains insufficiently understood. This review explores the influence of specific micronutrients—including selenium, iodine, and zinc—and dietary patterns, particularly the Mediterranean diet, on the pathophysiology of hypothyroidism and Hashimoto’s thyroiditis. We introduce a novel framework that integrates emerging data on sex-specific micronutrient interactions and nutritional immunomodulation. Unlike the existing literature, this review introduces original hypotheses related to sex-specific nutritional immunomodulation and proposes a novel framework for micronutrient-driven dietary intervention in Hashimoto’s thyroiditis. Full article

Hormonal contraceptives (HCs) are widely used and generally well tolerated; however, their neuroendocrinological effects remain underappreciated in clinical decision-making. Beyond ovulation suppression, HCs influence brain function by modulating key neurotransmitters such as GABA, serotonin, and dopamine, as well as neurosteroids like allopregnanolone and β-endorphin. These interactions help explain why some users experience mood swings, anxiety, or changes in sexual desire, while others report improvements in well-being. In this narrative review, we explore how different estrogenic and progestin components affect central pathways involved in emotional regulation and cognition. Evidence suggests that estradiol or estetrol-based formulations combined with anti-androgenic progestins like drospirenone or nomegestrol acetate may offer a more favourable neuroendocrine profile, particularly in women with a history of mood disorders or hormonal sensitivity. Understanding these neuroendocrine mechanisms may support more personalized contraceptive choices, particularly in women with mood disorders and hormonal vulnerability. Full article

The available literature data indicate that obestatin, a peptide derived from the preproghrelin precursor, may modulate neuroendocrine function, particularly in appetite regulation and somatotrophic/gonadotrophic pathways. This review synthesizes animal studies assessing the influence of obestatin on central neuroendocrine systems. Obestatin has been shown to affect the hypothalamic appetite-regulating center through neuropeptides such as neuropeptide Y and agouti-related peptide, yet findings remain inconsistent between species. In rodents, its effects on food intake and energy balance are inconclusive, whereas sheep models demonstrate significant alterations in orexigenic gene expression and peptide immunoreactivity. Regarding the somatotrophic axis, obestatin showed no significant effect on growth hormone (GH) secretion in rodents; however, in sheep, it modulated growth hormone-releasing hormone and somatostatin mRNA expression, elevated pituitary GH synthesis, and increased circulating GH levels. Studies involving the gonadotrophic axis demonstrated the presence of obestatin in Leydig and pituitary cells, with in vitro evidence suggesting its ability to modulate intracellular pathways implicated in gonadoliberin, luteinizing hormone, and follicle-stimulating hormone release. The collective findings discussed in this article indicate that obestatin interacts with multiple hypothalamic–pituitary axes, though its effects vary depending on species and experimental conditions. This review highlights the complexity of obestatin’s central actions and the need for further research to elucidate its functional relevance in neuroendocrine regulation. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article