Search Results (202)

Brassinosteroids (BRs) are steroid hormones that are essential for plant growth, development, and environmental adaptation. They control the division, elongation, and differentiation of various cell types throughout the entire plant life cycle, affecting growth and the stress response. Therefore, fine-tuning of BR biosynthesis and modulation of signaling pathways offer possibilities for developing cultivars characterized by adjusted plant architecture or improved stress tolerance to benefit crop production. Additionally, precise BR treatments can be employed to increase the productivity of crop plants. This review aims to provide a comprehensive summary of the genetic basis of traits related to BR metabolism and signaling in cucurbits, the second largest vegetable family, which contributes significantly to global vegetable production and nutritional security. We summarize the current knowledge concerning BR biosynthesis mutants, the role of BRs in stress mitigation, and the potential of the exogenous application of BRs to alleviate stress during cucurbit production. We also discuss how genes related to BR metabolism can be used to develop gene editing strategies to advance precision breeding in cucurbits. Full article

This study elucidates the role of the steroidogenic acute regulatory protein (StAR) in sex steroid hormone dynamics and the gonadal development of the commercially important marine bivalve ark shell Scapharca broughtonii. The sequence of the StAR gene was obtained and verified from the transcriptome of ark shell, then the tissue localization and expression pattern during the gonad development of the StAR gene were detected by in situ hybridization and quantitative real-time PCR, respectively. Additionally, the concentrations of three critical sex steroid hormones (progesterone, testosterone, and estradiol) were measured throughout gonadal development using enzyme-linked immunosorbent assay (ELISA). The results showed that the length of the coding region of StAR was 1446 bp, encoding 481 amino acids. The results of qRT-PCR showed that the expression of the StAR gene varied with gonadal development, increased from the early active stage to the development stage, and decreased from the mature stage to the spent stage. Notably, the expression level in ovaries was higher than that in testes, suggesting the potential involvement of StAR in sex differentiation and gonadal development. Additionally, the results indicated that progesterone, testosterone, and estradiol accounted for 80%, 10%, and 10% of the total hormone content in the gonads, respectively. Correlation analysis revealed a highly significant strong positive correlation between progesterone/estradiol levels and StAR gene expression, demonstrating that StAR serves as a key regulator in sex steroid hormone biosynthesis. These findings provide crucial molecular evidence for StAR-mediated steroidogenesis in bivalve reproduction, offering fundamental insights into invertebrate endocrinology. Full article

Background and Objectives: Regional and systemic analgesic techniques, such as erector spinae plane (ESP) block and opioid administration, implemented during cancer surgery, have been shown to influence immune responses and potentially affect cancer outcomes. Surgical stress and analgesic techniques used in cancer surgery—such as regional nerve blocks or systemic opioids—not only affect pain control but also influence immune and inflammatory pathways that may impact cancer progression. To understand the biological consequences of these interventions, metabolomic profiling has emerged as a powerful approach for capturing systemic metabolic and immunological changes, which are particularly relevant in the oncologic perioperative setting. In this study, we examined the impact of the ESP on the metabolomic profile, as well as levels of VEGF, cortisol, and CRP, in addition to its analgesic effects in breast cancer surgery. Materials and Methods: Ninety patients were placed into three different analgesia groups (morphine, ESP, and control groups). Demographic data, ASA classification, comorbidities, surgery types, and pain scores were documented. Blood samples were taken at preoperative hour 0, postoperative hour 1, and postoperative hour 24 (T0, T1, and T24). VEGF, cortisol, and CRP levels were measured, and metabolomic analysis was performed. Results: Study groups were comparable regarding demographic findings, comorbidities, and surgery types (p > 0.05). NRS scores of group ESP were lowest in the first 12 h period (p < 0.01) and ESP block reduced opioid consumption (p < 0.01). VEGF and cortisol levels of group morphine were similar to ESP at T24 (p > 0.05). Group ESP had lower VEGF and cortisol levels than the control at T24 (p = 0.025, p = 0.041, respectively.). The CRP level of group morphine was higher than both ESP and control at T24 (p = 0.022). Metabolites involved in primary bile acid, steroid hormone biosynthesis, amino acid, and glutathione metabolism were changed in group ESP. Conclusions: Metabolites in bile acid biosynthesis and steroid hormone pathways, which play a key role in immune responses, were notably lower in the ESP group. Accordingly, VEGF and cortisol peaks were more moderate in group ESP. In conclusion, we think that ESP block, which provides adequate analgesia, is an acceptable approach in terms of modulating immune responses in breast cancer surgery. Full article

Granulosa cell (GC) dysfunction contributes to diminished ovarian reserve (DOR). We collected GC and follicular fluid samples from the patients of normal ovarian reserve (NOR) and DOR. RNA-seq of GCs showed that cholesterol/sterol metabolism and biosynthesis and extracellular matrix organization were enriched in the DOR group. Metabolomics of follicular fluid revealed enrichment in steroid hormone biosynthesis, tryptophan metabolism, and fatty acid β-oxidation in DOR. The apoptosis rate was increased, whereas the proliferative rate was decreased in GCs of DOR. The Prussian blue staining rate was increased whilst GPX4 and SLC7A11 expression were downregulated in GCs of DOR. Mitochondrial morphology displayed the features of ferroptosis in GCs of DOR. FSHR, CYP19A1, NR5A1, and phosphorylated CREB levels were substantially downregulated in GCs, accompanied by increased androgen levels in follicular fluids in DOR. The key factors linked to the mevalonate pathway, HMGCR, SQLE, and SREBF2, were robustly increased in DOR. FSHR and NR5A1 levels were correlated with CYP19A1 levels, whilst CYP19A1 levels were positively correlated with GPX4 and SLC7A11 levels. Our findings indicate ferroptosis and dysregulation of cholesterol/sterol metabolism and biosynthesis occurrence in GCs of DOR, which might be associated with reduced FSHR signaling and decreased conversion of androgen to estrogen. Full article

Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains understudied. Hair follicle layer samples were collected directly from the crown region of female pattern hair loss (FPHL), male pattern hair loss (MPHL), and healthy adult women (control) groups. Microbial DNA was extracted and analyzed using Illumina 16S rRNA V3–V4 gene amplicon sequencing. Alpha-diversity and beta-diversity analyses and taxonomic and functional profiling were conducted through relative abundance, LEfSe, and PICRUSt2 analyses. The alpha-diversity analysis showed a significant decrease in microbial richness in the hair loss groups. Unweighted UniFrac-based beta-diversity analysis revealed significant clustering between the control group and the FPHL group. Taxonomic profiling and LEfSe analysis identified differences in microbial composition and biomarkers. PICRUSt2 analysis further revealed altered pathways related to porphyrin metabolism, fatty acid biosynthesis, and steroid hormone metabolism. Additionally, differences in microbiome composition and potential functions were found between the FPHL and MPHL groups. This study provides comprehensive insights into the hair follicle microbiome, revealing unique microbial patterns and functional alterations associated with FPHL. Understanding these microbiome characteristics may contribute to targeted approaches for addressing AGA. Further research is warranted. Full article

Background: The growth traits of donkeys from the same farm under the same feeding conditions often vary. Methods: In this study, Plasma hormone level and LC–MS-based metabolomics was used to identify the metabolic pathways and the key metabolites associated with the growth rate of Dezhou donkeys. Results: The level of IGF-1 in the SG was significantly higher than that in the FG. The differentially abundant metabolites were related mainly to lipid metabolism, in which arachidonic acid metabolism, linoleic acid metabolism and steroid hormone biosynthesis played key roles. The main differentially abundant metabolites 2,3-dinor-8-iso-PGF2α, 11-DH-TXB2, 8(R)-HPETE, PGJ2, c9, t11-CLA, 12,13-DHOME, 9,10-DHOME, 9(10)-EpOME, 13-HPODE, DHEAS, testosterone, and corticosterone played important roles in metabolic homeostasis and affected the adaptation of donkeys to cold environments. Conclusions: The present study revealed that the growth rate of donkeys is mainly influenced by their adaptation to the environment, providing a more in-depth study on the relationship between plasma metabolomics and growth rate in donkeys. Full article

Yak (Bos grunniens) is the main economic animal growing in the Qinghai–Tibet Plateau. Because of its poor growing environment, copper deficiency is common. Studies have shown that appropriate copper supplementation can improve the reproductive performance of heifers. In this study, the primary granulosa cells of yak were isolated, and different copper levels were established by adding copper chelator and copper sulfate. Biochemical, Western blot and transcriptome methods were used to reveal the mechanism of copper on the hormone secretion function of granulosa cells. The results showed that copper promoted hormone secretion by regulating the expression of steroid synthase such as StAR, CYP19A1 and CYP11A1. Transcriptome analysis showed that copper ion levels significantly affected the function of cells, and changes in copper ion level affected genes related to protein phosphorylation, lipid metabolism, lipid biosynthesis, steroid hormone synthesis and the MAPK pathway. In conclusion, copper can promote steroid hormone synthesis in the granulosa cells of yak follicles, and the MAPK signaling pathway may be involved. Full article

Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 μM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 μM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 μM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations. Full article

Egg production is a complex biological process closely linked to ovarian development and metabolic adaptation in laying hens. As the core reproductive organ, the ovary undergoes significant changes during different egg-laying stages. This study employed untargeted metabolomics to analyze metabolites in serum and ovarian tissues of hens at 20W and 30W. The results revealed that metabolic reprogramming in ovarian tissues was more pronounced than in serum. Shared metabolites between serum and ovarian tissues demonstrated coordinated interactions between systemic and local metabolic networks. The synthesis of prostaglandin E1 during lipid metabolism was identified as a key driver of ovulation and hormone production. Extracellular matrix remodeling and polyamine metabolism, particularly spermidine/spermine, enhanced cell adhesion and antioxidant capacity during ovarian development. These findings provide new insights into follicular development, ovulation regulation, and steroid hormone biosynthesis, while suggesting potential metabolic targets to improve poultry reproductive efficiency. Full article

Understanding the early molecular events driving oral carcinogenesis is vital for diagnosing oral squamous cell carcinoma (OSCC) promptly. While metabolic differences between oral leukoplakia (OLK), OSCC, and healthy oral mucosa have been reported, the metabolic changes distinguishing malignant transformed OLKs (MT-OLK) from non-transformed OLKs (NT-OLK) remain unexplored. Here, we examine the metabolomic profiles of 5 cases of MT-OLK and 15 of NT-OLK to identify key predictive molecules using untargeted high-performance liquid chromatography-mass spectrometry. The potentially discriminant compounds were highlighted through a robust statistical analysis workflow, and the dysregulated metabolic pathways were illustrated by enrichment analysis. Seventeen molecular features, primarily lipids—including phospholipids, oxidised lipids, cholesteryl esters, and fatty acids—were identified as discriminants between MT-OLK and NT-OLK across statistical and bioinformatic approaches. Pathway enrichment analysis revealed alterations in lipid metabolism, particularly fatty acid synthesis and degradation, steroid hormone biosynthesis, and glycerophospholipid metabolism. Predictive models showed high accuracy (AUC = 0.88) in distinguishing the two groups. This study suggests that metabolomics has the potential to differentiate between MT-OLK and NT-OLK by identifying candidate biomarkers that may contribute to the understanding of malignant transformation. Validation in larger cohorts is warranted to translate these findings into clinical practice. Full article

PEG400 is widely used as a pharmaceutical excipient in the biomedical field. Increasing evidence suggests that PEG400 is not an inert drug carrier; it can influence the activity of various drug-metabolizing enzymes and transporters, thereby affecting the in vivo process of drugs. It can also alleviate obesity and adipose tissue inflammation induced by a high-fat diet. In this study, we employed proteomics to investigate the impact of PEG400 on hepatic protein expression in rats. We found that over 40 metabolic enzymes were altered, with UDP-glucuronosyltransferase 1a9 (Ugt1a9) showing the most significant upregulation. This observation is consistent with our previous findings. KEGG pathway enrichment analysis revealed that PEG400 influences retinol metabolism, steroid hormone biosynthesis, drug metabolism, bile secretion, fatty acid degradation, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and pentose and glucuronate interconversions. Western blot and molecular docking were used to quantitatively analyze related proteins. The results demonstrated that PEG400 promotes the metabolism of retinol to produce retinoic acid; enhances bile secretion by upregulating bile acid synthesis and transporter proteins; and activates the PPARα signaling pathway to regulate the expression of fat metabolism-related proteins, thereby reducing lipid accumulation. Furthermore, as natural ligands for nuclear receptors, retinoic acid and bile acids may activate nuclear receptors and initiate the regulation of target gene expression. We found upregulation of the nuclear receptors PPARα, retinoid X receptor alpha (RXRα), and pregnane X receptor (PXR). RXRα can form a dimer with PPARα or PXR to regulate the expression of target genes, which may explain the changes in the expression of numerous metabolic enzymes. This study provides a comprehensive understanding of the effects of PEG400 on liver metabolism in rats, reveals its potential biological functions, and offers new insights into the application and development of PEG400. Full article

Probiotics have attracted increasing attention due to their benefits in terms of relieving gastrointestinal ailments, including constipation. This study evaluated the potential of Weizmannia coagulans BC99 for clinical remission of constipation in adults. In this randomized, double-blind, and placebo-controlled trial, 90 individuals with constipation were divided between a BC99 and a placebo group for an 8-week intervention duration. The spontaneous bowel movement (SBM) frequency, patient assessment of constipation symptoms (PAC-SYM), patient assessment of constipation quality of life (PAC-QOL), inflammatory cytokines, neurotransmitters, and serum metabolites were investigated before and after the intervention. The results showed that BC99 intervention significantly improved constipation symptoms and quality of life in adults with constipation, as evidenced by an increased SBM score and decreased PAC-SYM and PAC-QOL scores. Additionally, BC99 supplementation increased the levels of neurotransmitters (5-HT, MTL, AChE, and BDNF) associated with intestinal motility and alleviated inflammation in participants with constipation, as supported by higher levels of anti-inflammatory factors (IL-4, IL-10) and lower levels of pro-inflammatory factors (IL-6, IFN-γ) in the BC99 group. Furthermore, BC99 altered the abundance of 93 metabolites and affected biological pathways correlated with gastrointestinal motility, including sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism. This study demonstrates the effectiveness of the W. coagulans BC99 strain in relieving constipation in adults, and reveals its potential mechanism of action. These findings provide a scientific basis for BC99 as an effective and safe probiotic for constipation treatment. Full article

Objectives: Training is essential for enhancing equine athletic performance, but the genetic mechanisms that regulate athletic performance are unknown. Therefore, this paper aims to identify candidate genes and metabolic pathways for the effects of training on equine athletic performance through multi-omics analyses. Methods: The experiment selected 12 untrained trot-type Yili horses, which underwent a 12-week professional training program. Blood samples were collected at rest before training (BT) and after training (AT). Based on their race performance, whole blood and serum samples from 4 horses were chosen for transcriptomic and metabolomic analyses. Results: The race performance of the horses is dramatically improved in the AT period compared to the BT (p < 0.01) period. The transcriptome analysis identified a total of 57 differentially expressed genes, which were significantly enriched in pathways related to circadian entrainment, steroid hormone biosynthesis, chemokine signaling, and cholinergic synapses (p < 0.05). Additionally, metabolomic analysis revealed 121 differentially identified metabolites, primarily enriched in metabolic pathways such as histidine metabolism, purine metabolism, and the PI3K-Akt signaling pathway. The integration of transcriptomic and metabolomic analyses uncovered five shared pathways, and further combined pathway analyses identified eight differentially expressed genes that correlate with 19 differentially identified metabolites. Conclusions: The current findings will contribute to establishing a theoretical framework for investigating the molecular mechanisms of genes associated with the impact of training on equine athletic performance. Additionally, these results will serve as a foundation for enhancing the athletic capabilities of trot-type Yili horses. Full article

The greater amberjack (Seriola dumerili) is an emerging marine fish that is increasingly favored in aquaculture. Currently, there are few studies on the development and regulation of greater amberjack ovaries. In this study, the ovary transcriptome profiles of greater amberjack at three different stages (stage II, III, and IV) were performed, and identified the genes and pathways that may play significant roles in the processes of follicle growth and maturation. A total of 6597, and 1061 differentially expressed genes (DEGs) were detected in FII vs. FIII, FIII vs. FIV, and FII vs. FIV stages, respectively. GO and KEGG enrichment analyses revealed that these DEG_S are primarily involved in steroid hormone biosynthesis (e.g., cyp11a1, cyp17a1, cyp19a1a, hsd3b1, esr1), lipid metabolism (e.g., plpp3, lpl, pld1, and fabp10a), and meiotic arrest and resumption (e.g., pgr, arb, ccnd2, adcy2, adcy9, myl9, calm1). Additionally, several signaling pathways involved in ovarian development have been identified, including the PI3K-Akt, Wnt, TGF-beta, GnRH, and immune-related signaling pathways. qPCR results of nine representative genes related to steroid hormone synthesis and cell growth verified the reliability of the generated RNA-seq data. This research contributes to our comprehension of the molecular processes underlying ovarian growth and maturation in marine fishes and provides a theoretical basis for the investigation of functional genes associated with oogenesis in greater amberjack. Full article

Background: Gynecomastia, caused by an estrogen–testosterone imbalance, affects males across various age groups. With unclear mechanisms and no approved drugs, the condition underscores the need for efficient, innovative treatment strategies. Methods: This study utilized deep learning-based computational methods to discover potential drug compounds for gynecomastia. To identify genes and pathways associated with gynecomastia, initial analyses included text mining, biological process exploration, pathway enrichment and protein–protein interaction (PPI) network construction. Subsequently, drug–target interactions (DTIs) were examined to identify potential therapeutic compounds. The DeepPurpose toolkit was employed to predict interactions between these candidate drugs and gene targets, prioritizing compounds based on their predicted binding affinities. Results: Text mining identified 177 genes associated with gynecomastia. Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified critical genes and pathways, with notable involvement in signal transduction, cell proliferation and steroid hormone biosynthesis. PPI network analysis highlighted 10 crucial genes, such as IGF1, TGFB1 and AR. DTI analysis and DeepPurpose predictions identified 12 potential drugs, including conteltinib, yifenidone and vosilasarm, with high predicted binding affinities to the target genes. Conclusions: The study successfully identified potential drug compounds for gynecomastia using a deep learning-based approach. The findings highlight the effectiveness of combining text mining and artificial intelligence in drug discovery. This innovative method provides a new avenue for developing specific treatments for gynecomastia and underscores the need for further experimental validation and optimization of prediction models to support novel drug development. Full article