Search Results (436)

Chemical regulators play an important role in alleviating abiotic stress during seed germination and early seedling establishment, providing a low-cost and effective solution for crop production under stress conditions. The seed germination stage is critical for crop establishment under drought stress. Proso millet (Panicum miliaceum L.) is relatively drought-tolerant during later growth stages but remains sensitive during seed germination and early seedling establishment. In this study, two P. miliaceum varieties (‘Yumi 2’ and ‘Yumi 5’) were used as materials. Seeds were soaked with 2,4-epibrassinolide (EBR) at concentrations of 0, 0.01, 0.1, 0.5, and 1 μmol·L⁻¹, and then germinated under polyethylene glycol (PEG-6000) solutions at 0%, 15%, and 20% (w/v) to simulate drought stress. Drought stress progressively reduced seed germination potential, germination percentage, germination index, and vigor index, while increasing mean germination time and decreasing germination synchrony. EBR soaking, particularly at 0.01 μmol·L⁻¹, consistently alleviated the above inhibitory effects. Under 20% PEG stress, 0.01 μmol·L⁻¹ EBR increased the germination potential of ‘Yumi 5’ to 82% and significantly improved the germination percentage of both varieties. Compared with the control, low concentrations of EBR (0.01 and 0.1 μmol·L⁻¹) increased the germination synchrony of ‘Yumi 2’ by up to 89.5% and 93.6%. Under 20% PEG stress, the germination synchrony of ‘Yumi 2’ treated with 0.01 μmol·L⁻¹ EBR was 54.7% higher than that of the control. EBR treatment increased α-amylase activity, with the highest activity observed at 0.01 μmol·L⁻¹ under non-stress conditions, and it maintained relatively high activity under drought stress, especially in ‘Yumi 5’. The two varieties exhibited genotype-dependent response differences: ‘Yumi 5’ responded to a wider range of EBR concentrations under drought stress, whereas ‘Yumi 2’ showed a selective response. Soaking seeds with 0.01 μmol·L⁻¹ EBR is a promising pre-sowing treatment strategy for improving seedling establishment of P. miliaceum under drought-prone conditions. In summary, this study provides a low-cost and easily applicable hormone soaking method that can be directly used to enhance the early drought tolerance of cereal crops. Furthermore, this strategy may offer practical guidance for improving seedling techniques in medicinal plants facing similar drought stress during propagation, thereby supporting sustainable agricultural production in water-deficient regions. Full article

Background/Objectives: A recent Delphi survey of endocrinologists revealed low consensus regarding the diagnosis of pediatric growth hormone deficiency (GHD). Thus, we sought to describe the various trajectories undertaken by healthy 8–14-year-old youth in the 2 years following testing for GHD at a single major pediatric academic institution. Methods: Electronic health records were reviewed for the current analysis from healthy 8–14-year-old participants enrolled in a prospective longitudinal observational study of parent and youth characteristics associated with youth quality of life and self-esteem over a two-year period following growth hormone (GH) stimulation testing. Participants were grouped according to their peak GH concentration on testing (<7, 7–10, and ≥10 ng/mL), and outcomes included treatment (or not) with GH or other growth-altering hormonal treatments. Results: Of the 115 participants, 27 (23%) had peak GH < 7 ng/mL, 27 (23%) 7–10 ng/mL, and 61 (53%) peaked ≥ 10 ng/mL. Across the three groups, some patients were not offered GH treatment, some were offered yet did not pursue treatment, and some were offered and treated—with further variance provided by GH treatment interruptions, early cessation vs. continued GH treatment, delayed GH treatment start, and treatment with other agents (testosterone, gonadotropin-releasing hormone agonist, or aromatase inhibitor) either in lieu of or in addition to GH. Conclusions: Even within the network of a single academic institution, variability is evident in the management of healthy 8–14-year-old short youth following GH stimulation testing. Full article

Background/Objectives: The global landscape of growth hormone (GH) therapy is increasingly affected by supply shortages, posing risks to treatment continuity, particularly in rare diseases with a single authorized GH brand. In Italy, a prolonged shortage of the only approved recombinant human GH (rhGH) for SHOX-deficient (SHOXD) patients (Somatropin, Humatrope^®) raised concerns about treatment interruption. As growth impairment is a key clinical feature of SHOXD, uninterrupted rhGH therapy is essential. To address this issue, the Italian Medicines Agency (AIFA) temporarily authorized the off-label use of alternative rhGH formulations. This study aimed to evaluate growth outcomes and safety over one year of off-label rhGH treatment in SHOXD patients and to compare these data with prior Humatrope^® treatment. Methods: Fifty SHOXD patients (25 females), aged 2–17 and still in the growth phase, previously treated with Humatrope^®, were switched to an alternative rhGH therapy. Height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS) were recorded 12 and 6 months before and after the switch. Growth trends were analyzed using repeated-measures ANOVA. Results: No statistically significant differences in HSDS or HVSDS were observed after switching to alternative rhGH compared with prior treatment (p > 0.05). IGF-1 SDS values remained stable within age- and puberty-appropriate reference ranges. No adverse events were reported. Conclusions: In this real-world pediatric cohort, one year of off-label rhGH treatment during a drug shortage was not associated with relevant changes in growth parameters or safety concerns. These findings may support treatment continuity during temporary disruptions in rhGH availability. 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: Human growth hormone (hGH) deficiency (GHD) is typically treated with daily injections of recombinant human growth hormone (rhGH), which do not fully replicate physiological secretion patterns. This study evaluates a novel approach using synthetic mRNA encoding hGH encapsulated in lipid nanoparticles (LNPs) and designated VTRC-01 to enable endogenous hormone production. Methods: VTRC-01 was administered intramuscularly to hypophysectomized (Hypox) prepubertal Wistar rats, and its efficacy was compared with rhGH. A cohort of healthy rats was included to assess anabolic effects and safety. Results: VTRC-01 stimulated longitudinal growth in both Hypox and healthy rats, achieving effects comparable to rhGH. Treatment induced a significant anabolic response that exceeded the basal growth rate of healthy controls. Conclusions: These findings provide proof-of-concept for hGH mRNA-based therapy as a promising alternative to rhGH. Further improvements in mRNA and LNP technologies are expected to enhance safe hormone production. These promising results underscore the potential of reprogramming via therapeutic mRNA the synthesis of key endocrine regulators (such as hGH) directly within the organism, offering for the first time a powerful pathway for the potential treatment for endocrine therapies targeting growth hormone deficiency. Full article

Nitrogen (N) is an essential macronutrient for plant growth. NIN–like protein (NLP) transcription factors play important roles in nitrate signaling and response in plants. However, a comprehensive analysis of the NLP gene family in sorghum is still lacking. In this study, we identified five NLP genes in sorghum, and a high collinearity of NLP was detected in sorghum, rice and maize. N deficiency decreased SbNLP3 and SbNLP4 expression levels in roots, and the expression of SbNLP1 and SbNLP2 declined in roots during nitrate resupply. Subcellular localization analysis revealed that SbNLP1 was mostly detected in nuclei and cytoplasm. Compared with wild–type rice ZH11 plants, SbNLP1 overexpression plants showed improved low nitrogen (LN) tolerance, with longer roots and shoots under LN conditions. Transcriptome analysis between overexpression lines OE1–5 and ZH11 showed that 773 and 967 differentially expressed genes (DEGs) were identified in roots and shoots under LN conditions, respectively. In contrast, 674 and 1283 DEGs were identified in roots and shoots under normal nitrogen (NN) conditions, respectively. Thirty–seven N–related DEGs were identified in roots through GO enrichment under LN conditions, and terms of plant hormone signal transduction, biosynthesis of secondary metabolites and plant–pathogen interaction were identified through KEGG enrichment. WGCNA analysis also revealed plant hormone signal transduction pathways and plant pathogen interaction pathways in OE1–5 under LN conditions. These results provide a basis for N use efficiency (NUE) improvement in sorghum and functional analysis of SbNLPs. Full article

Background: Growth hormone deficiency (GHD) is one of the most common endocrine sequelae in survivors of pediatric medulloblastoma, largely resulting from hypothalamic–pituitary irradiation. Concerns regarding the oncologic safety of growth hormone (GH) replacement have historically limited its use. This study aimed to evaluate growth response to GH therapy and its potential association with tumor relapse in medulloblastoma survivors treated between 2000 and 2023. Methods: We conducted a retrospective single-center cohort study including 74 patients diagnosed with medulloblastoma before 18 years of age. GHD was confirmed by stimulation testing according to standard criteria. Auxological, endocrine, and oncologic data were collected longitudinally. Growth outcomes were compared among patients without GHD (n = 38), patients with untreated GHD (n = 13), and patients with GHD receiving GH treatment (n = 23). Relapse rates were assessed following GH initiation and compared with those of untreated patients. Results: GHD was diagnosed in 48.7% of patients. Baseline height SDS did not differ among groups. Patients with untreated GHD experienced a significant decline in height SDS (−1.93 ± 0.78), whereas GH-treated patients showed a significant increase (+0.39 ± 0.06; p < 0.0001). Final height SDS was significantly lower in untreated GHD patients (−2.45 ± 0.36) compared with GH-treated patients (−1.71 ± 0.68) and patients without GHD (−0.68 ± 0.24; p < 0.0001). No evidence of an increased risk of tumor relapse was observed in association with GH therapy during follow-up. Conclusions: GH replacement significantly improves growth outcomes in medulloblastoma survivors with confirmed GHD without apparent increase in relapse risk when initiated after stable remission. The early identification and multidisciplinary management of GHD are essential components of long-term survivorship care. Full article

Lilium longiflorum is a diploid lily species valued for its tolerance to humid–hot environments and pleasant fragrance. However, its poor cold hardiness and low bulb-forming capacity limit its cultivation. To overcome these deficiencies, autotetraploids were previously generated in our laboratory via somatic doubling. In order to expand the reproductive efficiency of the two, this study optimized in vitro regeneration and bulblet enlargement protocols. We analyzed the effects of various plant growth regulators and sucrose concentrations, alongside the expression of genes related to carbohydrate metabolism and hormone signaling. Results revealed divergent regenerative pathways: diploids favored direct organogenesis (optimal medium: MS + 30 g/L sucrose + 0.5 mg/L 6-BA + 0.2 mg/L NAA + 1.0 mg/L glyphosate), whereas tetraploids thrived via a TDZ-induced callus pathway (1/2 MS + 30 g/L sucrose + 1.0 mg/L NAA + 0.2 mg/L TDZ). During bulblet enlargement, diploids were predominantly regulated by IBA and prone to proliferation (optimal enlargement medium: MS + 60 g/L sucrose + 2.0 mg/L IBA), while tetraploids were sucrose-sensitive and prioritized single-bulb hypertrophy (MS + 60 g/L sucrose + 0.5 mg/L IBA + 0.1 mg/L 6-BA + 0.1 mg/L CPPU). qRT-PCR indicated that LlAGPS1, LlGBSSI, LlSWEET15, LlMYC2, and LlSAUR32 were highly expressed in tetraploids during rapid enlargement (24–36 d), suggesting a role in bulb hypertrophy, whereas upregulated LlSUS4 and LlCWIN3 in diploids correlated with proliferation. The study provides a practical technical reference for the industrialized propagation of high-quality L.longiflorum bulbs and provide a theoretical foundation for understanding ploidy-dependent development in Lilium. Full article

Background/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case–control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 µg/L; additionally, a lower cut-off of 7.0 µg/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 µg/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p < 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS > 0.91. A Naïve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients. Conclusions: Interpretation of GHST should include the patient’s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children. Full article

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high morbidity among survivors. Emerging evidence suggests that acute biochemical hypothalamic–pituitary axis disturbances, resulting from disruption of neuroendocrine regulation, are an underrecognized complication in the acute phase of aSAH. However, its correlation with clinical severity remains insufficiently explored. To investigate whether clinical severity of aSAH predicts acute biochemical pituitary-axis abnormalities and identify which hormonal axes are most affected in the acute phase. A prospective observational study was conducted at The National Institute of Neurology and Neurovascular Diseases, Bucharest (October 2024–March 2025) on 38 patients confirmed aSAH admitted within 48 h of symptom onset, of which 20 patients were included. Hormonal panels assessing adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), and antidiuretic hormone (ADH) were obtained prior to surgical intervention. Clinical severity was evaluated using the Glasgow Coma Scale (GCS), the Hunt and Hess (HH) scale, and the Modified Fisher Scale. Correlations between hormonal deficiencies and severity scores were analyzed using the Spearman correlation. Biochemical abnormality of the ACTH axis was most prevalent (75%), followed by ADH (50%) and TSH (40%), while GH deficiency was rare (5%). ACTH-axis biochemical abnormality correlated significantly with lower GCS (ρ = −0.61, p = 0.004) and higher HH scores (ρ = 0.59, p = 0.006). Multiple-axis abnormalities demonstrated the strongest correlations with all severity metrics (GCS: ρ = −0.68, p = 0.001; HH: ρ = 0.72, p < 0.001; Fisher: ρ = 0.57, p = 0.009). Greater clinical severity in aSAH is associated with a higher prevalence of acute biochemical endocrine abnormalities, particularly involving the ACTH axis and multiple hormonal pathways. These findings are exploratory and hypothesis-generating. Early hormonal assessment in patients with severe aSAH may help identify individuals at risk for acute endocrine abnormality, but validation in larger prospective studies is required before influencing clinical practice. Full article

Background: Growth hormone deficiency (GHD) in childhood impairs linear growth and may affect body composition, metabolism, and quality of life; recombinant human growth hormone (rhGH) therapy improves outcomes, but response is highly variable, especially in idiopathic GHD (IGHD). Objective: To summarize current evidence on predictors of growth response to rhGH therapy in children with IGHD, focusing on clinical, biochemical, and treatment-related determinants. Methods: This is a narrative review dealing with studies assessing clinical, auxological, biochemical and treatment-associated factors that may influence response to rhGH in IGHD. Results: Early treatment initiation, baseline short stature, prepubertal status, and higher early height growth velocity are strong clinical predictors; biochemical markers, including GH peak, IGF-1, and IGFBP-3, provide complementary information. Modifiable factors such as GH dose, adherence to therapy, and therapy duration also influence outcomes. Integrated predictive models improve accuracy but require further validation. Conclusions: Growth response to rhGH in IGHD is multifactorial and could be individualized: early identification of suboptimal responders and personalized treatment strategies that integrate clinical, biochemical, and treatment-related data may optimize the final outcome. Future research studies should focus on validated predictive models incorporating genetic and molecular markers. Full article

Advances in pediatric oncology have markedly improved survival, shifting attention toward long-term treatment-related morbidity. Targeted agents and immune-based therapies are now widely used across pediatric malignancies and selected non-malignant conditions, often for prolonged periods and during critical windows of growth and development. Because many therapeutic targets regulate physiological pathways involved in growth, pubertal maturation, gonadal function, bone metabolism, and energy homeostasis, clinically relevant endocrine toxicity may emerge during treatment or become apparent only with extended follow-up. This narrative review summarizes pediatric evidence on endocrine and metabolic effects associated with major classes of targeted and immune-based therapies, including tyrosine kinase inhibitors, mTOR inhibitors, MAPK-pathway inhibitors (BRAF/MEK), TRK inhibitors, ALK inhibitors, immune checkpoint inhibitors, and immune effector therapies. Distinct patterns of endocrine vulnerability emerge across drug classes: growth impairment and bone–mineral alterations are most consistently reported with tyrosine kinase inhibitors; weight gain and metabolic changes predominate with MAPK-, TRK-, and ALK-targeted agents; immune checkpoint inhibitors are characterized by early, multi-axis immune-related endocrinopathies with a high likelihood of permanent hormone deficiency once established. In contrast, endocrine abnormalities observed after immune effector therapies largely reflect indirect effects of systemic inflammation, corticosteroid exposure, and prior hematopoietic stem cell transplantation rather than direct endocrine toxicity. Given the limited pediatric-specific data, frequent confounding by multimodal therapy, and the potential for delayed or irreversible endocrine sequelae, structured endocrine monitoring and long-term survivorship care are essential for children exposed to modern anticancer therapies. Full article

Atherosclerosis is a complex, multifactorial disease that progresses through distinct stages: initiation, progression, and complication, ultimately leading to acute coronary syndromes (ACS). Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages are central players in this process, influencing plaque stability and vulnerability. Insulin-Like Growth Factor 1 (IGF-1), soluble-Klotho (S-Klotho), and the Growth Hormone Receptor exon 3 deletion polymorphism (GHRd3) have emerged as key modulators of vascular health, impacting these cellular components through various mechanisms. IGF-1 supports endothelial function, enhances VSMC survival and migration, and mitigates inflammation by inhibiting macrophage recruitment and activation, ultimately reducing the risk of plaque destabilization. S-Klotho, an anti-aging protein with potent anti-inflammatory and antioxidant properties, has been linked to vascular protection, with its deficiency associated with endothelial dysfunction, vascular calcification, and impaired VSMC survival. Evidence suggests that IGF-1 may enhance Klotho shedding, indicating a potential synergistic role in maintaining vascular integrity. This narrative review aims to outline the fundamental stages of atherosclerosis progression, consolidate current evidence on the roles of IGF-1 and S-Klotho in modulating key cellular components of atherosclerosis, and shed light on their potential involvement in plaque healing—an area that remains largely unexplored. By integrating established molecular mechanisms, we explore how these factors may contribute to endothelial integrity, VSMC survival, and macrophage activation and polarization, potentially shaping a more stable plaque phenotype and influencing future therapeutic strategies in cardiovascular disease. Full article

Background: Recombinant human growth hormone (rhGH) replacement therapy, administered to children with growth hormone deficiency (GHD), exerts pleiotropic effects on growth, metabolism, and tissue functions. Extracellular vesicles (EVs) are emerging mediators of inter-organ communication, but the effects of rhGH therapy on EV release in humans have not yet been investigated. Methods: In a preliminary prospective clinical study, children with GHD (n = 10; F/M = 5/5; age: 11.0 ± 2.7 years) were treated with rhGH for 6 months. Plasma samples were collected at baseline (T0) and after treatment (T6) to characterize the size distribution and tissue-derived composition of circulating EVs. Total EVs and EV subpopulations derived from monocytes/macrophages (CD14+), adipose tissue (FABP+), skeletal muscle (SCG+), endothelium (CD62E+), and platelets (CD42A+) were analyzed. Clinical, auxological/auxometric, and biochemical/metabolic parameters were assessed in parallel. Statistical methods included longitudinal analyses, interaction models, and adjustments for relevant covariates, including insulin-like growth factor 1 (IGF-1) and osteocalcin. Results: After 6 months of rhGH therapy, significant improvements in height velocity (cm/year and SDS) were observed, accompanied by increased circulating IGF-1 and osteocalcin levels. Hormone therapy induced no size-dependent changes in (total) EVs. Significant increases in CD14+ and FABP+ EVs were observed after treatment, without affecting the other tissue-derived EVs. Interaction analyses revealed that children with more severe GHD exhibited a stronger vesiculogenic response to rhGH. Furthermore, specific tissue-derived EVs were associated with metabolic/biochemical and auxological/auxometric parameters, including lipids, insulin resistance, and growth-related measures. Conclusions: When administered for six months, rhGH therapy seems to selectively change tissue-derived composition of circulating EVs in GHD children, particularly those derived from immune cells and adipose tissue. These preliminary findings suggest that EVs might represent an adjunctive component of GH-dependent inter-organ communication and might serve as biomarkers of treatment response and disease severity in pediatric endocrinology. Full article