Search Results (5,450)

Brassinosteroids (BRs) are essential regulators of plant development and stress responses, but the distinct contributions of BR biosynthesis and signaling to hormonal crosstalk remain poorly defined. Here, we investigated the effects of the BR biosynthesis inhibitor brassinazole (BRZ) and the BR-insensitive mutant bri1-6 on endogenous phytohormone profiles in Arabidopsis thaliana. Using multivariate analysis and targeted hormone quantification, we show that BRZ treatment and BRI1 disruption alter hormone balance through partially overlapping but mechanistically distinct pathways. Principal component analysis (PCA) and hierarchical clustering revealed that BRZ and the bri1-6 mutation do not phenocopy each other and that BRZ still alters hormone profiles even in the bri1-6 mutant, suggesting potential BRI1-independent effects. Both BRZ treatment and the bri1-6 mutation tend to influence cytokinins and auxin conjugates divergently. On the contrary, their effects on stress-related hormones converge: BRZ decreases salicylic acid (SA), jasmonic acid (JA), and abscisic acid (ABA) in the WT leaves; similarly, bri1-6 mutants show reduced SA, JA, and ABA. These results indicate that BR biosynthesis and BRI1-mediated perception may contribute independently to hormonal reprogramming, with BRZ eliciting additional effects, possibly via metabolic feedback, compensatory signaling, or off-target action. Hormone correlation analyses revealed conserved co-regulation clusters that reflect underlying regulatory modules. Altogether, our findings provide evidence for a partial uncoupling of BR levels and BR signaling and illustrate how BR pathways intersect with broader hormone networks to coordinate growth and stress responses. Full article

Background: Polycystic ovarian syndrome (PCOS) is one of the most prevalent reproductive, endocrine, and metabolic disorders inflicting women of childbearing age. Dietary interventions have gained interest as non-pharmacological approach to control obesity and metabolic disturbances. However, the effects of intermittent fasting (IF) on metabolic and hormonal profiles of PCOS patients is debatable. Objectives: We performed this systematic review and meta-analysis to explore IF’s effect on PCOS women’s metabolic and hormonal profile (PROSPERO: CRD42024511520). Eligible studies included IF interventions in women with PCOS, with metabolic and hormonal profiles being reported. Methods: A systematic literature search using three databases, including PubMed, SCOPUS, and Web of Science, was conducted. The systematic review was performed following PRISMA guidelines. Results: A total of four studies were included (N = 4). IF is not associated with significant change in BMI (MD = −0.200, 95% CI [−0.807, 0.407], p = 0.518). The analysis revealed that IF had no statistically significant impact on FBG (MD = −0.569, 95% CI [−9.955, 8.818], p = 0.906), HOMA-IR (MD = −0.862, 95% CI [−1.737, 0.014], p = 0.054), and FINS (MD = −2.749, 95% CI [−6.441, 0.943], p = 0.145). No significant change in TG (MD = −3.120, 95% CI [−9.624, 3.385], p = 0.347), total cholesterol (MD = −0.918, 95% CI [−2.960, 1.124], p = 0.378), and LDL levels (MD = −0.433, 95% CI [−1.224, 0.359], p = 0.284) between IF and pre-fasting or non-intervention diet groups. However, the explanation is limited by the small number of studies, duration of fasting regimes, and/or variations in fasting strategies. Sex hormone data were collected but were insufficient for a pooled analysis. Conclusions: Overall, our study suggests that IF is not an effective intervention to enhance BMI, glycaemic control, and lipid metabolism in PCOS patients. Nevertheless, the current conclusion is inconclusive and preliminary, as additional well-designed studies are required to support this conclusion. Full article

Background: Early detection of dysglycemia in young adults is important but underexplored. This study aimed to (1) predict long-term changes in fasting plasma glucose (δ-FPG) and (2) classify future prediabetes using complementary machine learning (ML) approaches. Methods: We analyzed 6247 Taiwanese men aged 18–35 years (mean follow-up 5.9 years). For δ-FPG (continuous outcome), random forest, stochastic gradient boosting (SGB), eXtreme gradient boosting (XGBoost), and elastic net were compared with multiple linear regression using Symmetric mean absolute percentage error (SMAPE), Root mean squared error (RMSE), Relative absolute error(RAE), and Root relative squared error (RRSE) Sensitivity analyses excluded baseline FPG (FPG_base). Shapley additive explanations(SHAP) values provided interpretability, and stability was assessed across 10 repeated train–test cycles with confidence intervals. For prediabetes (binary outcome), an XGBoost classifier was trained on top predictors, with class imbalance corrected by SMOTE-Tomek. Calibration and decision-curve analysis (DCA) were also performed. Results: ML models consistently outperformed regression on all error metrics. FPG_base was the dominant predictor in full models (100% importance). Without FPG_base, key predictors included body fat, white blood cell count, age, thyroid-stimulating hormone, triglycerides, and low-density lipoprotein cholesterol. The prediabetes classifier achieved accuracy 0.788, precision 0.791, sensitivity 0.995, ROC-AUC 0.667, and PR-AUC 0.873. At a high-sensitivity threshold (0.2892), sensitivity reached 99.53% (specificity 47.46%); at a balanced threshold (0.5683), sensitivity was 88.69% and specificity was 90.61%. Calibration was acceptable (Brier 0.1754), and DCA indicated clinical utility. Conclusions: FPG_base is the strongest predictor of glycemic change, but adiposity, inflammation, thyroid status, and lipids remain informative. A dual interpretable ML framework offers clinically actionable tools for screening and risk stratification in young men. Full article

The Nile tilapia (Oreochromis niloticus), a key aquaculture species, displays marked sexual growth dimorphism, with males growing faster than females. This process is governed by intricate interactions between antagonistic regulators, including transcription factors, growth factors, and steroid hormones, operating through sex-specific developmental pathways. While circular RNAs (circRNAs) are known to modulate gene expression by sponging microRNAs (miRNAs), their role in teleost sex differentiation remains poorly understood. To address this gap, we profiled circRNA expression in tilapia gonads by constructing six circRNA libraries from testes and ovaries of 180 days after hatching (dah) fish, followed by high-throughput sequencing. We identified 6564 gonadal circRNAs distributed across all 22 linkage groups, including 226 differentially expressed circRNAs (DECs; 108 testis-biased, 118 ovary-biased). Functional enrichment analysis linked their host genes to critical pathways such as cAMP signaling, cell adhesion molecules, and—notably—sexual differentiation processes (e.g., estrogen signaling, oocyte meiosis, and steroid hormone biosynthesis). Furthermore, we deciphered competing endogenous RNA (ceRNA) networks, uncovering circRNA–miRNA–mRNA interactions targeting germ cell determinants, sex-specific transcription factors, and steroidogenic enzymes. This study provides the first systematic exploration of circRNA involvement in tilapia sex differentiation and gonadal differentiation, offering novel insights into the post-transcriptional regulation of sexual dimorphism. Our findings advance the understanding of circRNA biology in fish and establish a framework for future studies on aquaculture species with similar reproductive strategies. Full article

The cereal cyst nematode, Heterodera avena, is responsible for substantial economic losses in the global production of wheat, barley, and other cereal crops. Extracellular enzymes, particularly those from the glycoside hydrolase 18 (GH18) family, such as chitinases secreted by Trichoderma spp., play a crucial role in nematode control. However, the genome-wide analysis of Trichoderma longibrachiatum T6 (T6) GH18 family genes in controlling of H. avenae remains unexplored. Through phylogenetic analysis and bioinformatics tools, we identified and conducted a detailed analysis of 18 GH18 genes distributed across 13 chromosomes. The analysis encompassed gene structure, evolutionary development, protein characteristics, and gene expression profiles following T6 parasitism on H. avenae, as determined by RT-qPCR. Our results indicate that 18 GH18 members in T6 were clustered into three major groups (A, B, and C), which comprise seven subgroups. Each subgroup exhibits highly conserved catalytic domains, motifs, and gene structures, while the cis-acting elements demonstrate extensive responsiveness to hormones, stress-related signals, and light. These members are significantly enriched in the chitin catabolic process, extracellular region, and chitinase activity (GO functional enrichment), and they are involved in amino sugar and nucleotide sugar metabolism (KEGG pathway enrichment). Additionally, 13 members formed an interaction network, enhancing chitin degradation efficiency through synergistic effects. Interestingly, 18 members of the GH18 family genes were expressed after T6 parasitism on H. avenae cysts. Notably, GH18-3 (Group B) and GH18-16 (Group A) were significantly upregulated, with average increases of 3.21-fold and 3.10-fold, respectively, from 12 to 96 h after parasitism while compared to the control group. Meanwhile, we found that the GH18-3 and GH18-16 proteins exhibit the highest homology with key enzymes responsible for antifungal activity in T. harzianum, demonstrating dual biocontrol potential in both antifungal activity and nematode control. Overall, these results indicate that the GH18 family has undergone functional diversification during evolution, with each member assuming specific biological roles in T6 effect on nematodes. This study provides a theoretical foundation for identifying novel nematicidal genes from T6 and cultivating highly efficient biocontrol strains through transgenic engineering, which holds significant practical implications for advancing the biocontrol of plant-parasitic nematodes (PPNs). Full article

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of bone-modifying agents. The aim of this study was to elucidate the pathogenesis of MRONJ through a comprehensive comparison of bone-metabolism-related factors in sera from patients with MRONJ and healthy controls. Methods: This study was a retrospective cross-sectional biobank analysis in which 31 patients in a non-MRONJ group and 10 patients in an MRONJ group were screened. Serum levels of 13 proteins (i.e., hormones, growth factors, and cytokines) related to bone metabolism were measured by simultaneous multi-parameter analysis using bead-based immunoassays. Results: The MRONJ group displayed suppressed bone metabolism with a background of chronic inflammation. In addition, a significant decrease in the expression of alkaline phosphatase liver/bone/kidney (p < 0.05, effect size of 0.46 (95% CI: 0.08 to 0.73)) and a significant increase (p < 0.05, effect size was −0.42 (95%CI: −0.72 to 0.01)) in the expression of tumor necrosis factor α were observed in the MRONJ group. Conclusions: These results may contribute to a better understanding of the etiology, pathophysiology, and progression of MRONJ. Full article

Paulownia trees are grown globally for their robust timber, agroforestry, and effective carbon dioxide drawdown. China possesses rich Paulownia germplasm resources, offering favorable material for the genetic improvement. Understanding the taxonomy and phylogenetic relationships of Paulownia species is essential for the advancement of germplasm innovation. In this study, we re-sequenced 67 typical accessions of 11 species within the Paulownia genus. A total of 16,163,790 high-quality single nucleotide polymorphisms (SNPs) were identified. Based on these markers, these accessions were classified into three groups: P. fortunei and P. lampropylla (Group I); P. tomentosa, P. fargesii, and P. kawakamii (Group II); and P. taiwaniana, P. jianshiensis, P. catalpifolia, P. elongata, P. ichangensis, and P. albiphloea (Group III). Using maximum likelihood estimation, population genetic structure analysis revealed that the 11 species originated from four different ancestral populations. The two predominant breeding species—P. fortunei and P. tomentosa—exhibit divergent origins: P. fortunei arose from hybridization between two ancestral species followed by complex admixture, whereas P. tomentosa retains a predominantly singular ancestral lineage, with traces of P. kawakamii. The genetic diversity (π) of P. tomentosa was 0.002588, which was considerably lower than that of P. fortune (0.004181) suggesting that P. tomentosa is subjected to a stronger breeding selection during the evolution than P. fortune. A total of 59 selected regions and 65 genes were identified by selective sweep analysis. These genes may be involved in biological processes such as morphological development and response to abiotic stress and hormonal activity regulation. These findings provide valuable references for further research on the genetic differentiation and adaptive evolutionary mechanisms of Paulownia species, laying a foundation for future germplasm innovation and variety improvement. Full article

Background: An artificial ovary has emerged as a novel alternative approach to prevent the reintroduction of cancerous cells after ovarian tissue autotransplantation. This study evaluates the ability of decellularized Wharton’s jelly (dWJ) to facilitate human ovarian follicle growth in a xenotransplantation model. Materials and Methods: Two transplanted groups were established; one consisted of a decellularized Wharton’s jelly/alginate (dWJ/Alg) composite, and an alginate (Alg) group was used as the control group. Each artificial ovary received approximately 20 partially isolated viable human ovarian follicles, subsequently undergoing xenotransplantation into ovariectomized, non-immunodeficient NMRI mice. Grafts were extracted at 1, 2, 4, or 5 weeks for comprehensive histological and immunohistochemical evaluations. Additionally, mouse blood serum was collected for hormonal analysis. Results: H&E staining confirmed granulosa cell proliferation and follicle growth in dWJ/Alg after 1 week of grafting. While human ovarian-like structures and cell proliferation were visible in other grafts, follicles were not observed. Conversely, immunohistochemical staining for Vimentin, Ki67, and CD45 confirmed the presence of human cells, proliferative cells, and inflammatory cells, respectively. However, hormonal assays revealed no significant difference in estrogen or progesterone levels between the experimental groups. Conclusions: It seems that Wharton’s jelly/alginate hydrogel can be used as an artificial niche for simulating the ovarian environment, effectively supporting the growth of xenotransplants of isolated human follicles. Full article

The giant panda (Ailuropoda melanoleuca) is a vulnerable animal in China, and it is crucial to improve the reproduction efficiency of the giant panda. Mate preference is an important part of natural mating. We hypothesized that AGS metabolites differ according to their mate preference. In this study, we determined estrus-associated hormone levels in the urine of 19 female giant pandas. After confirming estrus via hormone levels and behavioral observation, we collected environmental biomarkers for metabolomics analysis. A total of 19 samples were divided to two groups according to the mating preference of female giant pandas. Metabolomics analysis by LC-MS/MS showed that a total of 115 differentially expressed metabolites were identified, including 97 upregulated metabolites and 18 downregulated metabolites. We found that prostaglandin B2, palmitoylcarnitine, prostaglandin G2, and estrone may be the potential markers of female mate preference. Pathway enrichment analysis showed that steroid hormone biosynthesis, phenylalanine metabolism, and tropane, piperidine, and pyridine alkaloid biosynthesis were the top three pathways. These results revealed the physiological changes in female giant pandas during mate preference trials, providing a perspective for understanding their chemical communication system reliant on anal gland secretions and improving the success rate of natural mating of giant pandas. Full article

Background: The relationship between total cholesterol (TC) levels and mortality in older adults is complex and may differ from younger populations. While hypercholesterolemia is a known midlife risk factor, this association may weaken or reverse with age. Biological differences in cholesterol metabolism—particularly hormonal changes—may contribute to sex-specific mortality risks, but this remains underexplored. We examined the association between TC and all-cause mortality in older adults, assessing sex-specific differences. Methods: We used data from the InCHIANTI study, a longitudinal, population-based study conducted in Tuscany, Italy. From the original cohort (N = 1453), 999 participants ≥65 years with baseline TC and mortality data were included. TC levels were categorized as <200 mg/dL, 200–239 mg/dL, and ≥240 mg/dL. The primary outcome was all-cause mortality over 6-years. Kaplan–Meier curves and Cox proportional hazards models assessed mortality risk across TC categories in the overall population and by sex. Restricted cubic splines explored non-linear associations. Models were adjusted for age, sex (only in overall population), BMI, physical activity, diabetes, COPD, hypertension, eGFR, polypharmacy and frailty. Results: A threshold effect was observed: mortality risk rose sharply below ~200 mg/dL and remained stable above. Compared to the <200 mg/dL group, intermediate and high TC levels were associated with lower mortality risk (HR 0.72; 95% CI: 0.53–0.99 and HR 0.71; 95% CI: 0.49–1.02, respectively). In sex-stratified analyses, this pattern was pronounced in women but weaker and not statistically significant in men. Results held after excluding statin users and were confirmed by spline analysis. Conclusions: In older adults, particularly women, low TC may signal underlying vulnerability, including malnutrition or inflammation. Full article

Background: Bisphenols (BPs) are present in medical instruments, plastic containers, and personal care products (PCPs). Bisphenol A has been replaced by its alternatives, bisphenol S, F, AF, and B. Due to the awareness of their toxicity, mixed exposure to these alternatives at the regional level has been given less attention; there is a need to study this area of research. This meta-analysis examined the exposure of urinary bisphenol A and its metabolites to blood Hypothalamic–Pituitary–Thyroid axis hormones (HPT axis hormones) in pregnant women and adult males and females. We searched Embase, PubMed, Web of Science, Cochrane Library, and CINAHL until 8 January 2025, yielding 4588 articles using the PECO framework. Quality assessment was done using AHRQ: Agency for Healthcare Research and Quality for cross-sectional and NOS: Newcastle Ottawa Scale for cohort studies, with combined exposure evaluated using random and fixed-effect models. The I² test assessed heterogeneity. We included eighteen studies for the final analysis. Fixed-effect model estimates revealed that BPA is negatively associated with thyroid-stimulating hormone (TSH) in female and male adults (β = −0.02; 95% CI = −0.04 to −0.01); (β = −0.08; 95% CI = −0.14 to −0.02). In Females, BPA was positively associated with free thyroxine, FT4 (β = 0.001, 95% CI, 0.001 to 0.001). In the male group, BPA was negatively associated with FT4 (β = −0.001, 95% CI, −0.001 to −0.001). As per pregnant women, there was no association found between exposure to bisphenols and total Thyroxine (TT4), FT4, and TSH in both trimesters (β = 0.010, 95% CI = −0.030 to 0.050); (β = 0.001, 95% CI = −0.010 to 0.010); (β = −0.001, 95% CI = −0.010 to 0.001), respectively, for early pregnancy. Bisphenols can significantly influence HPT axis hormones in adult males, females, and pregnant women. Gender-based studies were observed, concluding that adult females are more affected by bisphenol exposures than adult males. The subgroup analysis based on the regions did not reveal any associations. Full article

Background: There are no comparative trials between the two most common schemes in HER2-positive early breast cancer treatment; BERENICE (with anthracyclines) and TRAIN-2 (without anthracyclines). In this study, we investigated the pathological complete response (pCR) and safety events achieved with each. Methods: This analytical retrospective observational study included 111 patients with early and locally advanced HER-2-positive breast cancer who initiated neoadjuvant treatment with an anthracycline-based scheme (four cycles of doxorubicin and cyclophosphamide, followed by four cycles of taxane, trastuzumab, and pertuzumab = AC-THP) and a non-anthracycline scheme (carboplatin, weekly paclitaxel, trastuzumab, and pertuzumab for six–nine cycles = TCbHP) at the National Cancer Institute in Colombia, between April 2020 and December 2024. The primary endpoint was the pCR. Safety was analyzed in patients who received at least one treatment cycle. Results: A total of 51 patients received AC-THP and 60 TCbHP (89.6% of which received six cycles). The pCR was 58.3% in ACHTP and 60.4% in TCbHP (p = 0.84). As a descriptive analysis, with the anthracycline-based scheme, there was a trend toward a higher pCR in patients with T3-T4, positive nodal involvement (N+), and positive hormone receptor (HR+). Cardiac toxicity events during the neoadjuvant phase were 9.8% in ACTHP and 3.3% in TCbHP. Grade 2 neuropathy events were higher in patients with the TCbHP scheme, at 23.3%, versus 9.8% in ACTHP. Conclusions: We found similar pCR rates between the schemes with anthracyclines and without anthracyclines. It is still pertinent to discuss the risk–benefit of using anthracycline-based regimens in patients with HR+, T3-T4, and N+. The cardiac adverse events reported in our patients were similar to those reported in the BERENICE trial. Full article

Endocrine cells are dedicated to the production and processing of hormones, from peptides to small molecules, to regulate key physiological processes, including glucose homeostasis and metabolism. Because of this relatively high productivity, endocrine cells must handle a variety of stresses from oxidative stress to the unfolded protein response of the endoplasmic reticulum (UPR^ER). While much is known about the major pathways regulating the UPR^ER, the roles of endocrine cell type-specific, context-dependent, and time-dependent transcriptional changes are not well explored. To identify unique and shared responses to the UPR^ER across a subset of endocrine cell types, we tested representative lines for β-cells (insulin), α-cells (glucagon), δ-cells (somatostatin), X/A-cells (ghrelin), L-cells (glucagon-like peptide 1 (GLP1)), and thyrotropes (thyroid hormone and thyroglobulin). We exposed each cell type to the canonical ER stressor thapsigargin for 6 and 24 h, or vehicle for 24 h, and performed mRNA sequencing. Analysis of the data showed all lines responded to thapsigargin. Comparisons of differentially expressed genes between each line revealed both shared and unique transcriptional signatures. These data represent a valuable mineable set of candidate genes that may have cell type-specific functions during the UPR^ER and have the potential to lead to a new understanding of how different endocrine cells mitigate or succumb to ER stress. Full article

Objectives: Emerging evidence suggests that propolis possesses significant anti-obesity properties. While gut hormones and microbiota are known to play crucial roles in obesity development, the specific mechanisms through which propolis exerts its effects via the gut hormone axis remain poorly characterized. Methods: A high-fat diet (HFD) rat model was established to investigate the regulatory effects of propolis. After 10 weeks of intervention, blood serum, liver, colon tissues, and luminal contents were analyzed for metabolic parameters, gene expression of gut hormones and AMPK pathway markers, microbial community structure, and short-chain fatty acid production. Results: Propolis effectively mitigated HFD-induced metabolic disturbances, including excessive weight gain, adipose tissue accumulation, hyperlipidemia, and hepatic dysfunction. These improvements were associated with significant upregulation of the AMPK pathway. Importantly, propolis enhanced intestinal barrier integrity and differentially modulated gut hormone expression by increasing the mRNA levels of Cck, Gip, and Ghrl, and decreasing Lep and Gcg levels. 16S rRNA sequencing analysis revealed that propolis administration selectively enriched butyrate- and propionate-producing bacterial species. Correlation analysis further identified the Eubacterium brachy group as a pivotal microbial mediator in the propolis-modulated gut microbiota–gut hormone–liver AMPK axis. Conclusions: Our findings establish that propolis ameliorates obesity-related metabolic disorders by orchestrating crosstalk among gut microbiota, enteroendocrine hormones, and hepatic AMPK signaling. These results elucidate a novel mechanistic pathway in rodents; however, their direct translatability to humans requires further clinical investigation. This tripartite axis offers a mechanistic foundation for developing microbiota-targeted anti-obesity therapies. Full article

Terpene synthases (TPS) facilitate terpenoid production, influencing the flavor, color, and medicinal properties of Crocus sativus (saffron), a triploid geophyte of significant commercial importance. Despite its importance, the CsTPS gene family remains poorly characterized, limiting genetic enhancements in saffron’s agronomic features. This research performed a comprehensive genome-wide analysis of CsTPS genes using genomic, transcriptomic, and in silico approaches. BLASTP and PfamScan discovered thirty CsTPS genes, demonstrating conserved TPS domains, varied exon–intron architectures, and chromosomal clustering indicative of tandem duplications. Phylogenetic research categorized these genes into five subfamilies (TPS-a to TPS-e), with the prevalence of TPS-a suggesting a role in sesquiterpene biosynthesis. RNA-seq data (PRJNA976833, PRJNA400472) revealed tissue-specific expression, with CsTPS1 and CsTPS5 expressed in reproductive tissues and CsTPS2 in vegetative tissues. Stress-responsive genes (CsTPS1, CsTPS4) exhibited upregulation in response to cold and pathogen stress, with cis-regulatory elements (e.g., ARE, ABRE) indicating hormone control. The in-silico validation of CsTPS1, chosen for its elevated GMQE score (0.89), included primer design, ePCR, and vector optimization for expression in Arabidopsis thaliana. This study elucidates the contribution of the CsTPS family to saffron terpenoid diversity, providing a foundation for enhancing flavor, yield, and stress tolerance through genetic engineering. Full article