Search Results (15,841)

Clubroot disease, caused by Plasmodiophora brassicae, poses a serious threat to global Brassica crop production. Orphan genes (OGs), which are species or lineage-specific and lack detectable homologs in other taxa, have been implicated in various biotic stress responses. Here, we identified a novel Brassica rapa-specific orphan gene, designated CROG1, that confers resistance to clubroot. Heterologous overexpression of CROG1 in Arabidopsis thaliana significantly enhanced resistance to P. brassicae. Transcriptomic profiling of CROG1-overexpressing lines highlighted the essential role of the phenylpropanoid biosynthesis pathway, showing upregulation of key lignin synthesis genes (including CCoAMT, CAD6, PER4, and AZI1) and defense-related regulators (RBOHC and WAKs). Weighted co-expression network analysis further corroborated the link between CROG1-mediated resistance and enhanced lignin deposition and cell wall reinforcement. Our findings establish CROG1 as a Brassica-specific orphan gene that enhances clubroot resistance via phenylpropanoid pathway activation. These results highlight the potential of orphan genes as novel genetic resources for breeding clubroot-resistant Brassica varieties, offering a sustainable strategy to mitigate yield losses caused by this devastating disease. Full article

The GRF (Growth-Regulating Factor) gene family has indispensable regulatory functions in the morphological and physiological development of plants. Nonetheless, comprehensive investigations of GRF gene family members and their functional roles in Cymbidium goeringii, Cymbidium ensifolium, and Cymbidium sinense are still lacking. Therefore, the GRF gene family members in three Cymbidium species were systematically identified, and their expression profiles and potential biological functions were comprehensively evaluated in the study. The results provided evidence that eleven, eleven, and nine GRF genes were identified in C. goeringii, C. ensifolium, and C. sinense, respectively. These genes encode proteins considered as 153–584 amino acids and have been postulated to be located in the cell nucleus. The promoter contains cis-acting elements associated with hormone response regulation, tissue-specific expression, modulation of organismal growth and development, and environmental signal response. The analyses of gene architecture and motif composition demonstrated that introns and motifs within each evolutionary branch are highly similar, whereas significant differences exist between evolutionary branches. The results of chromosome localization and collinearity analysis showed that only a pair of segmental duplication genes was identified in C. goeringii. Moreover, transcriptome data and qRT-PCR results indicated that GRF genes are involved in various organs of C. goeringii. In conclusion, these findings may establish a foundation for theoretical inquiry into the future functional analysis of GRF genes in orchids. Full article

Plants have the ability to perceive a wide range of light spectra, from which they derive not only the energy required for photosynthesis but also a variety of environmental cues and signals mediated by specific photoreceptors that trigger a cascade of biochemical reactions essential for their development. The olive tree (Olea europaea L.) is a woody species for which, despite its agronomic and economic relevance, the influence of light on its development remains poorly understood. The present study, a combined approach was employed, involving the phenotyping of 10 different cultivars exposed exclusively to red light (RL) and blue light (BL) for a period of two months, in addition to the monitoring of expression profiles of 10 photoreceptor-encoding genes in two of the cultivars that exhibited the most contrasting responses to the different light conditions. Our results revealed a correlation between the expression of specific genes and the differential response to exclusive exposure to the two light spectra, highlighting a generally enhanced photosynthetic activity of nearly all cultivars to blue light (BL) and, conversely, a negative response to red light (RL). Taken together, our data, by elucidating the response of the olive to specific light spectra and the underlying molecular mechanisms, pave the way for further studies on these traits, which could be useful for the improvement of this species. Full article

Background: Breast cancer, particularly the luminal subtype, often responds to endocrine therapies. However, 20–30% of patients develop resistance, resulting in more aggressive disease. Long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. Objective: This study aimed to evaluate the role of the lncRNA insulin-like growth factor 2 antisense (IGF2-AS) in tamoxifen-resistant breast cancer and assess its potential as a therapeutic target. Methods: Two tamoxifen-resistant breast cancer cell lines (TAMR-V and TAMR-H) were used to assess IGF2-AS expression via qPCR. Knockdown experiments with siRNA evaluated the role of IGF2-AS in cell proliferation, invasion, and migration. Next-generation sequencing (NGS) analyzed gene expression differences between the cell lines. Kaplan–Meier survival analysis determined the clinical significance of IGF2-AS expression in breast cancer patients. Results: IGF2-AS expression was significantly upregulated in TAMR-V and TAMR-H cell lines compared to control MCF-7 cells. Knockdown of IGF2-AS reduced cell proliferation and invasion in TAMR-V cells but did not significantly affect TAMR-H cells, indicating a cell line-specific role in tamoxifen resistance. NGS revealed differential gene expression profiles between TAMR-V and TAMR-H cells, suggesting variability in resistance mechanisms. Survival analysis demonstrated that higher IGF2-AS expression was associated with poorer prognosis in breast cancer patients, including those with hormone-positive and triple-negative subtypes. Conclusions: IGF2-AS is upregulated in tamoxifen-resistant breast cancer and promotes cell proliferation and invasion in a cell line-specific manner. Its differential expression in TAMR-V and TAMR-H cells highlights the complexity of resistance mechanisms, suggesting IGF2-AS as a potential therapeutic target for overcoming tamoxifen resistance. Full article

Background: Prostate cancer (PCa) is the primary contributor to male cancer-related mortality and currently lacks effective treatment options. The Modified Guizhi Fuling Decoction (MGFD) is used in clinical practice to treat multiple tumors. This research focused on the mechanisms of action (MOA) in MGFD that inhibit PCa. Methods: The impact of MGFD on PCa cells (PC3 and DU145) was examined via Cell Counting Kit-8, wound healing assays, and transwell assays. To determine the MOA, high-throughput sequencing based high-throughput screening (HTS²) was utilized along with network pharmacology. Results: The findings indicated that MGFD suppressed the proliferation, migration, and invasion of PCa cells. We then utilized the HTS² assay to generate 270 gene expression profiles from PCa cells perturbed by MGFD. Large-scale transcriptional analysis highlighted three pathways closely associated with PCa: the TNF signaling pathway, cellular senescence, and FoxO signaling pathway. Through the combination of network pharmacology and bioinformatics, we discovered four primary targets through which MGFD acts on PCa: AKT serine/threonine kinase 1 (AKT1), Caspase-8 (CASP8), Cyclin-Dependent Kinase 1 (CDK1), and Cyclin D1 (CCND1). Finally, molecular docking demonstrated that the potential bioactive compounds baicalein, quercetin, and 5-[[5-(4-methoxyphenyl)-2-furyl] methylene] barbituric acid strongly bind to CDK1, AKT1, and CASP8, respectively. Conclusions: This research shows that MGFD displays encouraging anticancer effects via various mechanisms. Its multi-target activity profile underscores its promise as a potential therapeutic option for PCa treatment and encourages additional in vivo validation studies. Full article

Potassium (K) is a critical macronutrient for sugarcane (Saccharum spp.), playing a vital role in metabolic processes, sucrose accumulation, and yield formation. Herein, this study systematically evaluated the effects of potassium oxide (K₂O) application on sugarcane (cultivar YZ1696) growth at the seedling and tillering stages. Hydroponic experiments demonstrated that 6 mmol/L K₂O optimally promoted seedling growth, whereas field trials revealed that 150 kg/ha K₂O maximized growth rate, yield, and sucrose content. Sugarcane growth exhibited a biphasic response—stimulation followed by inhibition—with increasing K₂O dosage at both developmental stages. Transcriptomic profiling of sugarcane roots under low-potassium (K-deficient), optimal potassium, and high-potassium conditions identified 10,266 differentially expressed genes (DEGs), with the most pronounced transcriptional shifts occurring under K deficiency. Functional enrichment analysis identified DEGs associated with potassium transport, calcium signaling, and carbohydrate metabolism. Notably, potassium uptake was mediated by distinct mechanisms: Shaker family channels (AKT1, AKT2, SPIKE) and the TPK family member KCO1 were induced under optimal K supply, whereas HAK/KUP/KT transporters (HAK1/5/10/21/25) exhibited broad activation across K concentrations, underscoring their key role in K homeostasis. Furthermore, calcium signaling genes (e.g., CIPK23) displayed K-dependent expression patterns. Weighted gene co-expression network analysis identified key gene modules that correlated strongly with agronomic traits, including plant height, yield, and sucrose content. Optimal K conditions favored the expression of yield- and sucrose-associated genes, suggesting a molecular basis for K-mediated productivity enhancement. Our findings revealed the genetic and physiological mechanisms underlying K-dependent sugarcane improvement, providing actionable insights for precise potassium fertilization to maximize the yield and sugar content. Full article

To investigate the impacts of dietary Bacillus-based probiotics and yeast-derived prebiotics on the hepatic transcriptome profile, 500 Hisex White laying hens were randomly allotted into five dietary treatments from 37 to 52 weeks of age: control; control + Bacillus subtilis; control + Bacillus subtilis and Bacillus licheniformis; control + Bacillus coagulans; and control + Saccharomyces cerevisiae yeast cell wall. Transcriptome analysis revealed a substantial number of differentially expressed genes exclusively between the control and prebiotic groups, identifying 2221 genes (FDR ≤ 0.05), with 980 genes upregulated (log₂ fold change 0.69 to 24.62) and 1241 downregulated (log₂ fold change −0.74 to −26.46). The top 10 upregulated KEGG pathways included protein export, glycerophospholipid metabolism, tryptophan metabolism, amino acid biosynthesis, alanine, aspartate, and glutamate metabolism, cofactor biosynthesis, propanoate metabolism, ABC transporters, 2-oxocarboxylic acid metabolism, and protein processing within the endoplasmic reticulum. In contrast, the most prominently downregulated pathways encompassed fructose and mannose metabolism, hedgehog signaling, PPAR signaling, Notch signaling, GnRH signaling, cell adhesion molecules, cytokine–cytokine receptor interactions, apelin signaling, glycosaminoglycan degradation, and RIG-I-like receptor signaling. These findings advance understanding of the hepatic transcriptomic response to yeast-derived prebiotics and identify key molecular pathways that could be targeted to enhance metabolic function in laying hens. Full article

Objective: Insulin resistance (IR) is a complex and multifactorial disorder that contributes to type 2 diabetes and cardiovascular disease. MicroRNAs (miRNAs) play important roles in diverse developmental and disease processes. However, the molecular mechanisms of IR are unclear. This paper aims to explore the role of miRNA in regulating IR and to elucidate the mechanisms responsible for these effects. Methods: IR models were created by feeding a high-fat diet (HFD) to mice or stimulating 3T3-L1 cells with palmitate. Twelve weeks of HFD trigger weight gain, leading to lipid accumulation and insulin resistance in mice. The expression profiles of miRNAs in adipose tissues (AT) from the HFD-induced mouse models were analyzed. The relationship between miR-221-3p and SOCS1 was determined using dual luciferase reporter gene assays. Metabolic alterations in AT were investigated by real-time PCR and Western blot. Results: miR-221-3p was significantly increased in AT. HFD-induced disturbances in glucose homeostasis were aggravated by miR-221-3p upregulation. The inhibition of miR-221-3p promoted insulin sensitivity including reduced lipid accumulation and the disruption of glucose metabolism. Of note, the 3′-UTR of SOCS1 was found to be a direct target of miR-221-3p. The SOCS1 inhibitor attenuated miR-221-3p-induced increases in IRS-1 phosphorylation, AKT phosphorylation, and GLUT4. miR-221-3p was considered to be involved in the PI3K/AKT signaling pathway, thus leading to increased insulin sensitivity and decreased IR in HFD-fed mice and 3T3-L1 adipocytes. Conclusions: The miR-221-3p/SOCS1 axis in AT plays a pivotal role in the regulation of glucose metabolism, providing a novel target for treating IR and diabetes. Full article

Dendrobium officinale, an orchid of significant medicinal and ornamental value, exhibits poorly characterized hormonal regulation of flower bud differentiation. To address this knowledge gap, we employed an integrated multi-omics approach combining physiological, transcriptomic, metabolomic, and network analyses to elucidate the molecular mechanisms underlying the coordinated action of 6-Benzylaminopurine (6-BA) and Gibberellin A3 (GA₃) in this critical developmental process. Our key findings reveal that combined 6-BA and GA₃ treatment significantly enhances flower bud differentiation and induces stage-specific fluctuations in soluble sugar, protein, and starch levels. Transcriptomic profiling identified 11,994 differentially expressed genes (DEGs), with DEGs specific to the hormone-treated stage showing pronounced enrichment in plant hormone signal transduction and plant–pathogen interaction pathways. Metabolomic analysis uncovered 18 stage-specific differential metabolites (DAMs) during hormone treatment, including GA₃, 6-BA, and OPDA, whose accumulation dynamics were strongly correlated with the progression of differentiation. Weighted gene co-expression network analysis (WGCNA) pinpointed key hub genes within the yellow module, notably transcription factors from the C2H2, bZIP, and NAC families. Their interaction network demonstrated significant correlation with the transcriptional regulation of hormone-responsive genes. Significantly, this study establishes the first molecular framework for 6-BA and GA₃ regulation of flower bud differentiation in D. officinale. We demonstrate a metabolomic–transcriptomic coordination network driven by these hormones, where key hub genes form regulatory modules with transcription factors. Dynamic shifts in endogenous hormones reinforce the flowering signal. These findings provide crucial molecular targets for precision flowering control and molecular breeding strategies in orchids. Full article

Fusarium head blight (FHB), caused by Fusarium graminearum (F. graminearum), has become one of the most devastating wheat diseases, severely impacting both grain yield and quality. The resistance gene TaHis (encoding a histidine-rich calcium-binding protein), located at the major FHB resistance locus Fhb1, has been demonstrated to confer FHB resistance in wheat, although its underlying mechanism remains unclear. In this study, we screened a wheat yeast two-hybrid (Y2H) library and identified TaU11/U12-35K, a core component of the U12-type spliceosome (U11/U12 small nuclear ribonucleoprotein), as a novel interacting partner of TaHis. Their physical interaction was further confirmed by both Y2H and bimolecular fluorescence complementation assays. Barley stripe mosaic virus-induced gene silencing (BSMV-VIGS)-mediated knockdown of TaU11/U12-35K significantly enhanced FHB resistance in both resistant (Bainong 4299) and susceptible (Bainong 5819) cultivars compared to controls. Expression profiling revealed that TaU11/U12-35K was significantly downregulated upon F. graminearum infection in both cultivars, with consistently lower basal expression levels in Bainong 4299, suggesting a negative correlation between TaU11/U12-35K expression and FHB resistance. Collectively, our results demonstrate that TaU11/U12-35K physically interacts with TaHis and functions as a negative regulator of FHB resistance. This study provides new insights into the molecular mechanism of TaHis-mediated FHB resistance in wheat. Full article

Papillary thyroid cancer (PTC) is linked to obesity, but the biological mechanisms that may explain this connection have been only partially described. Potential factors that combine overweight/obesity with this cancer should be searched for in the immune pathways and chronic inflammation onset. In this study, we evaluated the role of the immune system in patients affected by PTC and stratified them according to Body Mass Index (BMI). An analysis of the expression profiles of >700 immune-related genes was performed in 36 PTCs, subdivided into four categories: underweight (A), normal weight (B), overweight (C), and subjects living with obesity (D). B was considered a reference category. In our study, the immune microenvironment of PTCs did not seem strongly influenced by BMI. However, based on the interaction from in silico protein–protein analysis, we found that the dysregulation profiles of groups A or D were similar as concerns pathways involved in T-cell differentiation, macrophage activation, regulation of the cell cycle, and senescence processes. Furthermore, we found significant downregulation of HMGB1 in the A and D categories, with upregulation of ARG2 in the D category. Although further studies are necessary, these genes may provide an opportunity to better understand immunometabolism in thyroid cancer. Full article

Background: It is established that depression significantly contributes to tumor development, yet its molecular link to gastric cancer progression remains unclear. Methods: In this study, we examined depression-related gene expression profiles in relation to clinical prognosis and identified estradiol and the NOTCH3 gene as critical factors involved in gastric cancer progression in the context of depression. Using a chronic unpredictable stress-induced tumor-bearing mouse model, we validated the impact of depression on tumor development. Additionally, the underlying molecular mechanisms were explored through a range of biological techniques, including Western blotting, immunofluorescence, flow cytometry and immunohistochemistry. Results: Depression significantly accelerated gastric cancer growth in our mouse model, characterized by decreased estradiol levels and increased NOTCH3 expression. Importantly, exogenous estradiol supplementation effectively counteracted depression-induced tumor growth. Consistently, in vitro studies showed that estradiol treatment suppressed NOTCH3 expression in HGC-27 and YTN3 cell lines. Furthermore, NOTCH3 was shown to modulate intracellular reactive oxygen species levels by regulating SOD2 activity, thereby influencing cell proliferation. Conclusions: This work identified the estrogen/NOTCH3 signaling as a key link between depression and gastric cancer development, offering promising therapeutic strategies to improve outcomes for patients suffering from psychological disorders. Full article

Urothelial carcinoma in situ (UCIS) is a high-grade non-muscle-invasive neoplasm with significant clinical implications due to its potential for progression to muscle-invasive disease. Accurate diagnosis and risk stratification are crucial for appropriate management, particularly given the variability in response to intravesical Bacillus Calmette-Guérin (BCG) therapy. While the diagnosis of UCIS primarily relies on morphological criteria, immunohistochemical (IHC) markers serve as valuable ancillary tools, particularly in challenging cases. Markers such as CK20, CD44, p53, and Ki-67 have been extensively studied, though none demonstrate complete sensitivity or specificity. Additionally, molecular classification has identified luminal and basal subtypes, with potential prognostic and therapeutic implications. Recent studies have also explored predictive biomarkers for BCG response, including PD-L1, whose expression correlates with recurrence and potential responsiveness to immune checkpoint inhibitors. Emerging targeted therapies, such as enfortumab vedotin, have shown promise, with nectin-4 overexpression observed in most UCIS cases. Despite these advancements, challenges remain, including interobserver variability in morphological assessment, heterogeneous IHC methodologies, and the need for standardized molecular testing. This review highlights the current understanding of diagnostic, prognostic, and predictive tissue biomarkers in UCIS, underscoring the potential role of molecular profiling in guiding personalized treatment strategies. Future research should focus on refining biomarker-driven classification systems to improve risk stratification and therapeutic decision-making in UCIS patients. Full article

Recent years have witnessed a concerning rise in early-onset eating disorders (EDs), prompting a re-evaluation of their etiology, diagnosis, and treatment within pediatric populations. This perspective article synthesizes emerging evidence on the multifactorial origins of EDs in children, emphasizing a biopsychosocial framework that integrates genetic, epigenetic, psychological, and environmental factors. While early manifestations often diverge from adolescent or adult profiles—marked by somatic complaints, selective eating, and ritualistic behaviors—the disorders significantly interfere with developmental milestones. The COVID-19 pandemic has further exacerbated vulnerabilities, acting as a catalyst for disordered eating behaviors through increased familial stress, isolation, and disrupted routines. Central to this framework is the role of parental psychopathology and parent–child feeding interactions, which profoundly shape children’s emotional regulation and attachment patterns. Recent studies also underscore genetic susceptibilities—especially variants in the DRD4 and DAT1 genes—and epigenetic modifications that may mediate the transmission of risk across generations. The article reviews evidence from observational and genomic studies, highlighting how altered gene expression linked to early environmental stress contributes to the heterogeneity of EDs. Finally, it evaluates prevention and intervention strategies, including family-based treatments, digital health tools, and school-based programs. These strategies are essential for timely detection, individualized care, and reducing long-term impairment. Overall, the paper advocates for a nuanced understanding of EDs in children—recognizing their complex origins and developmental implications—to inform clinical practice, public health policy, and future research in pediatric mental health. Full article

Background: Tacrolimus is a cornerstone of immunosuppressive therapy following heart transplantation. Despite routine therapeutic drug monitoring (TDM), substantial interindividual variability in tacrolimus pharmacokinetics presents a persistent challenge. Pharmacogenetic profiling—particularly of CYP3A5 and CYP3A4 polymorphisms—offers a promising approach to individualize tacrolimus dosing and improve clinical outcomes. Case Presentation: We describe a 54-year-old male heart transplant recipient with persistently subtherapeutic tacrolimus trough concentrations despite escalating standard doses. Tacrolimus dosing initially started at 3.5 mg twice daily, escalated to 7.0 mg twice daily, with final maintenance dosing at 6.5 mg twice daily. TDM values were persistently subtherapeutic at 3–5 ng/mL for over a month before achieving therapeutic targets >10 ng/mL. Pharmacogenetic testing revealed a CYP3A5 expresser genotype (*1/*3) and normal CYP3A4 activity (*1/*1), suggesting enhanced metabolic clearance. In accordance with CPIC guidelines, tacrolimus dosing was intensified and supported by co-administration of diltiazem (60 mg twice daily, later adjusted to 90 mg twice daily), a CYP3A4 inhibitor. Subsequent TDM confirmed achievement of therapeutic levels. At nine months post-transplant, the patient exhibited stable graft function and excellent clinical status. Discussion: This case underscores the value of genotype-informed tacrolimus dosing in clinical scenarios where standard TDM is insufficient. Pharmacogenetic variation—particularly involving CYP3A5 expression—has been consistently associated with altered tacrolimus exposure and dose requirements. The literature supports routine genotyping in solid organ transplant recipients, although implementation remains limited. Additional considerations include drug–drug interactions, notably with CYP3A-modulating agents such as diltiazem and antifungals, which may further influence tacrolimus pharmacokinetics. Current evidence suggests that the utility of CYP3A4 genotyping may be phase-dependent, being more impactful during early post-transplant periods. Conclusions: Incorporating pharmacogenetic data alongside TDM facilitates more precise and individualized tacrolimus therapy, optimizing immunosuppressive efficacy and minimizing risk. This case, supported by literature review, advocates for broader integration of genotype-guided strategies in transplant pharmacotherapy. Full article