Search Results (2,949)

Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation. Full article

Cyclin-dependent kinases (CDKs) and cyclins are master regulators of the cell cycle, playing critical roles in plant growth, development, and stress responses. While these gene families have been extensively studied in model plants, a comprehensive analysis in soybean remains underexplored. To address this gap, we performed a genome-wide identification and systematic analysis of these families in soybean using bioinformatic approaches. Expression profiles and protein interactions of selected GmCDK and GmCyclin candidates were tested by qRT-PCR and BiFC assays. A total of 28 GmCDK and 101 GmCyclin genes were identified, revealing a significant expansion compared to Arabidopsis, rice, and maize, primarily driven by whole-genome and segmental duplications. Phylogenetic analysis classified GmCDKs into seven conserved clades (CDKA-CDKG) and GmCyclins into ten distinct subfamilies. Expression profiling demonstrated dynamic, tissue-specific patterns, with distinct modules active during seed development and in tissues. Promoter analysis further linked these genes to hormonal and stress-responsive pathways. Crucially, BiFC assay identified specific interactions between GmCDKA2, GmCDKA3, GmCDKB1 and GmCYCA3-3, suggesting evolutionary divergence in soybean CDK-Cyclin regulatory networks. This study provides a foundational resource for the soybean cell cycle regulome, highlighting its evolutionary plasticity and implicating specific CDK-Cyclin pairs as potential targets for manipulating agronomic traits such as seed development and stress resilience. Full article

Background/Objectives: Treatment intensification with novel hormonal therapies is now standard in metastatic hormone-sensitive prostate cancer (mHSPC), but real-world patients are often more heterogeneous than those included in pivotal trials. This study aimed to describe clinical characteristics, safety, treatment discontinuation, disease progression, polypharmacy, and clinically documented drug–drug interactions in a real-world mHSPC cohort. Methods: We conducted a retrospective observational study including 109 patients with mHSPC who initiated abiraterone, enzalutamide, apalutamide, or docetaxel-based triplet regimens between January 2015 and November 2025. Outcomes included adverse events, discontinuation, PSA50 response at 3 months, time to progression and overall survival. Descriptive analyses and Kaplan–Meier estimates were performed. Results: Apalutamide was the most frequent first-line treatment (56.9%), followed by abiraterone (23.9%), enzalutamide (11.9%), darolutamide-based triplet therapy (3.7%), and abiraterone-based triplet therapy (3.7%). Median age was 73 years, and median baseline PSA was 16.1 ng/mL. De novo metastatic disease was present in 69.7% of patients, ISUP grade 4–5 disease in 58.7%, high-risk disease according to LATITUDE criteria in 45.9%, and high-volume disease according to CHAARTED criteria in 38.5%. The median Charlson Comorbidity Index was 4, and polypharmacy was observed in 68.8%. Adverse events occurred in 56.0%, and non-death treatment discontinuation occurred in 22.0%. No documented drug–drug interactions requiring treatment modification were recorded. PSA50 response was achieved by 97.2%. Thirteen patients (11.9%) progressed and 18 (16.5%) died. Median time to progression was not reached, and median overall survival was 53.2 months. Conclusions: Novel hormonal therapies were used in a clinically heterogeneous real-world mHSPC cohort. The findings support individualized treatment assessment and should be interpreted as descriptive and exploratory. Full article

Southern corn leaf blight (SCLB), caused by Bipolaris maydis, poses a serious threat to maize production worldwide. In our previous study, Bacillus velezensis BV3 was isolated and demonstrated strong antagonistic activity against maize leaf spot pathogens and effective disease control in greenhouse experiments. In this study, we evaluated the plant growth-promoting effects of BV3 on two maize cultivars through root application in pot experiments, and investigated the underlying molecular mechanisms using transcriptomic and metabolomic analyses. Inoculation with BV3 significantly promoted maize growth. Moreover, BV3 treatment induced extensive transcriptional and metabolic reprogramming in maize. Transcriptomic analysis identified numerous differentially expressed genes (DEGs) mainly enriched in plant–pathogen interaction, plant hormone signal transduction, MAPK signaling pathway, and phenylpropanoid biosynthesis pathways. Metabolomic analysis revealed substantial changes in metabolite accumulation, particularly in lipids, amino acids, sugars, organic acids, and polyphenols, with enriched pathways including secondary metabolite biosynthesis, phenylpropanoid biosynthesis, and flavonoid biosynthesis. LC/MS and GC/MS analyses further revealed that BV3 produced diverse bioactive compounds. 2,4-DTBP and surfactin exhibited strong antifungal activities, particularly against B. maydis and Exserohilum turcicum. Overall, Bacillus sp. BV3 exhibits strong biocontrol efficacy against maize leaf spot pathogens and significant plant growth-promoting activity, highlighting its potential as an eco-friendly biocontrol agent for the management of southern corn leaf blight. Full article

The hallmark feature of empty follicle syndrome (EFS) is failure to retrieve oocytes from apparently mature follicles despite adequate ovarian stimulation and appropriate ovulation triggering. Although considered uncommon, with a reported prevalence ranging from 0.2% to 7%, EFS may have a profound clinical and psychological impact and can recur in assisted reproductive technology (ART) cycles. Modern classification systems divide EFS into genuine and false forms. Genuine EFS is potentially associated with intrinsic abnormalities involving luteinizing hormone/choriogonadotropin receptor (LHCGR) signaling, oocyte competence, and cumulus–oocyte interaction, whereas false EFS is primarily attributed to pharmacokinetic or pharmacodynamic factors resulting in inadequate trigger exposure. Borderline EFS represents a third phenotype characterized by incomplete or partial impairment of final oocyte maturation. This review examines the pharmacodynamics of ovulation-triggering agents, including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) agonist protocols, and dual-trigger strategies, and their roles in regulating final oocyte maturation. The molecular aspects of periovulatory signal transduction and the mechanisms of LHCGR activation, epidermal growth factor (EGF)-like pathways, and meiotic resumption in relation to EFS etiopathogenesis will be described. The impact of patient-dependent conditions like obesity, poor ovarian reserve, polycystic ovary syndrome (PCOS), and pituitary response on trigger response will be assessed. New approaches like post-trigger monitoring of hormones and rescue treatment with gonadotropins represent a valuable method for avoiding cycle cancellation in patients at risk. Overall, EFS is increasingly regarded not as a single disorder but as a heterogeneous spectrum of periovulatory dysfunction arising from pharmacological, endocrine, and intrinsic ovarian factors that impair completion of final oocyte maturation. Full article

Vegetative propagation is widely used in forest plantations to propagate elite genotypes with traits of economic or ecological interest. However, the loss of the ability to form adventitious roots is a dramatic effect of tree age and maturation and represents a major limitation for the clonal propagation of high-quality genotypes. This review describes the evolution of our understanding—from the traditional role of plant growth regulators to current findings on cellular signaling—regarding the maturation-related decline of adventitious rooting in forest species. Evidence suggests that interactions between the cell wall, plasma membrane, and cytoskeleton play a key role in this process. Specific and dynamic modifications of the interactions between the cell wall and cytoskeleton could be possible targets for hormonal, developmental, environmental, and epigenetic regulation associated with the maturation-related decline in adventitious root formation. Full article

Cardiovascular disease is the leading cause of death in women, yet prevention and management have historically relied on male-centered models. Sex and gender critically influence risk, clinical presentation, and outcomes. Depression, anxiety, and psychosocial stress, more prevalent in women, act as key amplifiers of cardiovascular risk. We conducted a clinically oriented narrative review based on a broad, non-systematic search of major databases, integrating evidence selected for relevance and methodological robustness to clarify biological and psychosocial mechanisms linking mental health and cardiovascular disease in women. Affective disorders and stress contribute to cardiovascular risk through interconnected pathways, including hormonal fluctuations, autonomic and neuroendocrine dysregulation, inflammation, endothelial dysfunction, and heightened platelet reactivity. These mechanisms interact with gender-related exposures such as caregiving burden, occupational stress, and interpersonal violence. Stress-related phenotypes, including mental stress, induced ischemia and takotsubo syndrome, exemplify the heart-brain axis and its clinical implications. Incorporating mental health into cardiovascular risk assessment is essential for precision prevention in women. A women-centered approach should include systematic psychosocial evaluation, multidisciplinary care, and tailored strategies to improve risk control, adherence, and outcomes. Full article

The Cytochrome P450 (CYP) superfamily plays an important role in the regulation of plant growth and development. However, the composition, evolutionary characteristics, and potential functions of CYPs in celery remain largely unexplored. Therefore, the objective of this study was to perform a genome-wide characterization of the Apium graveolens Cytochrome P450 (AgCYP) gene family and investigate its potential roles in seed development. In this study, a total of 227 AgCYPs were identified, and phylogenetic analysis classified them into six clades. Conserved motif and domain evaluations indicated that most AgCYP proteins possess conserved P450 domains. Chromosomal localization revealed an unequal distribution of AgCYPs across the 11 celery chromosomes. Duplicated AgCYP gene pairs were identified by synteny and Ka/Ks analyses, indicating that the duplicated AgCYPs have undergone strong purifying selection. Inter-genomic synteny analysis further reflects the closer relationship within Apiaceae. Analysis of cis-acting elements in the promoter regions identified an abundance of elements associated with light, hormone, and environmental stress. Moreover, AgCYPs showed stage-specific expression patterns and were correlated with monoterpene and phthalide accumulation during celery seed development, suggesting their potential functions in secondary metabolism in seed development. Treatment with exogenous auxin and its transport and biosynthesis inhibitors differentially induced distinct expression responses among AgCYPs, indicating their possible participation in auxin-related regulatory pathways. Moreover, candidate genes were selected. They exhibited diverse tissue-specific expression patterns and were potentially localized to the endoplasmic reticulum and interacted with some auxin-related proteins. In conclusion, this study provides the first comprehensive framework for understanding the functional diversification of AgCYPs in celery seeds, providing new insights into the evolutionary features and biological functions of the AgCYP gene family and establishing a foundation for future functional studies and molecular breeding applications. Full article

Laccases (EC 1.10.3.2, LAC) are copper-containing glycoproteins involved in lignin biosynthesis, and as such, they play important roles in plant development and stress responses. In this study, a genome-wide analysis of the LAC gene family was performed in Pinus massoniana (Chinese red pine), identifying 78 PmaLAC genes, all predicted to encode cell membrane-localized proteins. These genes were unevenly distributed across eight chromosomes, with notable clusters on chromosomes 7 and 8, indicating gene duplication-driven expansion in P. massoniana. Phylogenetic analysis revealed that PmaLAC genes are classified into five subfamilies, reflecting the lineage-specific expansion and evolutionary divergence of gymnosperm LAC genes. Conserved motif and gene structure analyses showed high conservation among PmaLAC proteins. Promoter analysis identified numerous cis-acting elements related to hormone signaling, stress, and light responses. RNA-seq analysis revealed distinct tissue-specific expression patterns for PmaLAC gene family members. Moreover, degradome analysis combined with dual-luciferase assays supported the interaction between miR397c-9 and PmaLAC31, suggesting that miR397c-9 negatively regulates PmaLAC31 and indicating a potentially conserved miRNA-mediated regulatory mechanism. Overall, this study provides a systematic overview of the composition, evolution, and potential regulation mechanisms of the PmaLAC gene family in P. massoniana, providing a useful resource for future functional characterization of PmaLAC genes. Full article

Background/Objectives: Cytokinin and auxin are essential for vascular development in plants. This study aims to explore whether these two hormones exhibit crosstalk in the cambium, analogous to that observed in the apical meristem. Methods: Using the hybrid poplar (Populus alba × Purshia glandulosa clone ‘84K’), we integrated gravitropic induction with transcriptomic analysis and identified the cytokinin biosynthesis gene PagIPT5 as differentially expressed in a tension wood induction system. PagIPT5 overexpression lines were generated and assessed for growth-related phenotypes. The interaction between cytokinin and auxin was investigated via anatomical observation, cell proliferation assays, in situ PCR, and immunofluorescence detection of auxin and cytokinin. Results: Compared with the wild type, PagIPT5 overexpression lines showed growth inhibition and an auxin-deficient phenotype. High PagIPT5 expression in the vascular cambium elevated cytokinin levels while reducing auxin levels, leading to decreased cambial cell proliferation and suppressed xylem development. However, in the tension wood induction system, both auxin and cytokinin levels increased in the vascular cambium of tension wood relative to opposite wood. Treatment with a superoxide anion activator promotes the accumulation of both auxin and cytokinin in 84K plants. Conclusions: These results revealed an antagonistic interaction between the two hormones in the cambium zone. However, this antagonism is attenuated in tension wood, which may be induced by the accumulation of superoxide anion in tension wood. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and male hypogonadism (HG) are prevalent disorders that frequently coexist, suggesting a bidirectional “liver–testis axis” as a potential pathophysiological link. This review explores the mechanistic basis and clinical implications of this axis. Molecularly, metabolically stressed hepatocytes release an altered hepatokine signature—marked by reduced sex hormone-binding globulin (SHBG) and elevated fibroblast growth factor 21 (FGF21)—along with pro-inflammatory cytokines (e.g., interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), which enter the systemic circulation. These factors may contribute to the impairment of Leydig cell steroidogenesis, the perturbation of blood–testis barrier integrity, and the disruption of spermatogenesis. Conversely, testicular dysfunction and subsequent testosterone deficiency promote visceral adiposity, worsen insulin resistance and amplify chronic inflammation, thereby accelerating hepatic steatosis and fibrosis. Clinically, these molecular interactions manifest as mutually worsening of MASLD and HG. Thus, the liver–testis axis establishes a framework that reveals the bidirectional crosstalk between hepatic metabolism and gonadal function, providing novel pathophysiological insights into these interconnected conditions. Full article

Background: Breast cancer is the most common malignancy among women and a leading cause of cancer-related deaths globally. Its development involves hormonal, genetic, environmental and inflammatory factors. Among environmental contributors, cadmium (Cd²⁺), a metalloestrogen known to induce redox imbalance, as well as estrogen metabolites, may exert divergent biological effects. Methods: This study investigated the effects of 17β-estradiol (E2) and its metabolites—2-methoxyestradiol (2-MeOE2) and 4-hydroxyestradiol (4-OHE2)—administered alone or in combination with CdCl₂, on estrogen receptor–-positive MCF-7 breast cancer cells and their doxorubicin-resistant cells (MCF-7/DOX). We evaluated cytotoxicity, interaction profiles (synergism/antagonism), and redox-related enzymes associated with drug resistance, including superoxide dismutase 1 (SOD1) and glutathione S-transferase pi (GST-pi). There are no known examples of these types of interactions, especially those involving estrogen metabolites with opposing biological activities—anticancer 2-MeOE2 and procarcinogenic—4-OHE2 in combination with cadmium. Cell viability was assessed after 48 h exposure to individual and combined treatments of CdCl₂. Interaction types (synergism/antagonism) were determined via the combination index method. Antioxidative enzymes were evaluated by quantitative and immunocytochemical analysis of SOD1, GST and GST-pi expression. Results: All tested compounds reduced cell viability in a concentration-dependent manner, with CdCl₂ showing the highest cytotoxicity. MCF-7 cell lines were generally more sensitive to CdCl₂, E2, and 2-MeOE2, whereas MCF-7/DOX cell lines exhibited greater sensitivity to 4-OHE2. Combination studies revealed predominantly antagonistic interactions, particularly for CdCl₂ + 2-MeOE2, suggesting a protective redox-modulating effect of this metabolite. Resistant cells consistently displayed higher SOD1 activity and GST-pi expression, indicating enhanced adaptive responses to oxidative stress. Conclusions: Our study underscores the importance of concentration-dependent interactions between environmental Cd²⁺ and pathways regulated by 17β-estradiol and its metabolites, particularly in the context of cytotoxicity and redox imbalance relevant to breast cancer progression and therapy resistance. Full article

Adaptogens are substances touted for their ability to promote resilience to stress. With more individuals reporting a greater degree of perceived stress, renewed attention has been focused on novel adaptogen complexes for stress reduction. Salidroside is a potent adaptogen found in the Rhodiola root, traditionally credited with increasing resistance to physical and mental stressors, while recent science has uncovered the neuroprotective effects of L-malic acid. The main objective of this study was to determine if daily supplementation of a novel salidroside and L-malic acid complex, across two dosing levels, could improve markers of perceived stress and its downstream effects, including anxiety and sleep disturbance. A 6-week randomized, double-blind, placebo-controlled, clinical study was conducted on individuals who subjectively reported a 30% room for improvement in perceived stress. Post hoc subgroup analysis was also conducted to determine if subpopulations experienced any enhanced benefits. Clinically meaningful improvements were reported in perceived stress and anxiety across the study population. Furthermore, men and non-premenopausal women saw enhanced benefits in emotional appraisal and sleep, suggesting hormonal interactions may be an underlying factor. SalidroPRO™ is a new dietary ingredient complex that may support rapid and sustained psychological well-being. Full article

This study aims to determine the effect of an education intervention on female athletes’ menstrual health knowledge, communication, and perceived importance of menstrual cycle tracking, and whether factors such as age, education level, or hormonal contraceptive use influence these outcomes. Three athlete cohorts engaged in two workshops and received targeted handouts. Participants (n = 51) completed surveys before, after, and 3 months following the intervention, which included a menstrual health knowledge assessment and a series of ratings to ascertain perceived knowledge; likelihood that they would discuss menstrual health with teammates, coaches, medical staff, and performance staff; and perceived importance of menstrual cycle tracking. Bayesian generalised linear mixed models and Bayesian linear mixed models were used to understand the effect of time and interactions between time and age, educational level, or hormonal contraceptive use. Actual and perceived knowledge and likelihood to communicate with teammates and performance staff appeared to be higher post-intervention and were retained for at least three months. The importance of menstrual cycle tracking increased from post-intervention to follow-up, while no change in communication with coaches or medical staff was observed. There appeared to be some effect of age, education level, and hormonal contraceptive use on knowledge and communication with medical staff. A menstrual health education intervention could be a practical and effective strategy to promote menstrual health literacy and communication in sport settings. Full article

Selective androgen receptor modulators (SARMs) are commonly described as tissue-selective anabolic agents, yet the extent to which this selectivity is reflected at the level of receptor-binding energetics remains uncertain. This study evaluated the receptor interaction profiles of the steroidal SARM YK11 and the nonsteroidal SARM ostarine across five steroid hormone nuclear receptors. Flexible molecular docking was performed with AutoDock 4.2 against the androgen (AR), estrogen (ER), progesterone (PR), glucocorticoid (GR), and mineralocorticoid (MR) receptors, using testosterone, estradiol, progesterone, cortisol, and aldosterone as endogenous reference ligands. Binding free energy, docking-derived inhibition constants, intermolecular interaction energies, conformational sampling, and two-dimensional interaction maps were analyzed. Ostarine showed favorable binding across all receptor systems, with binding energies ranging from −10.42 to −12.05 kcal/mol and no pronounced energetic preference for the androgen receptor. YK11 displayed stronger predicted binding, particularly toward the glucocorticoid, progesterone, and androgen receptors, with a docking energy trend of GR > PR > AR > MR > ER. Interaction analysis revealed conserved polar anchoring residues across receptor pockets, together with scaffold-specific contacts that may explain cross-receptor compatibility. These findings indicate that, within the AutoDock 4.2 flexible docking framework applied in this study, docking-derived binding energies primarily describe thermodynamic compatibility with nuclear receptor ligand-binding domains and should not be interpreted as direct predictors of functional SARM tissue selectivity. The observed discordance between predicted receptor affinity and the established tissue-selective pharmacology of ostarine highlights the need for caution when using single-method docking workflows to infer selectivity among closely related steroid hormone receptors. The novelty of this study lies in demonstrating, using a defined AutoDock 4.2-based comparative protocol, that receptor-binding energetics alone do not recapitulate the functional tissue-selective behavior attributed to SARMs. Full article