Search Results (3,038)

Tetrabromobisphenol A (TBBPA), a widely utilised brominated flame retardant, demonstrates toxicological effects in aquatic organisms. Tea polyphenols (TPs), natural compounds found in tea leaves, exhibit both antioxidant and anti-inflammatory activities. The kidney is one of the major metabolic organs in common carp and serves as a target organ for toxic substances. This study evaluated the therapeutic potential of TPs in mitigating TBBPA-induced nephrotoxicity in common carp. Common carp were exposed to 0.5 mg/L TBBPA in water and/or fed a diet supplemented with 1 g/kg TPs for 14 days. In vitro, primary renal cells were treated with 60 μM TBBPA and/or 2.5 μg/L TPs for 24 h. Methods included histopathology, TUNEL assay for apoptosis, ROS detection, and molecular analyses. Antioxidant enzymes (SOD, CAT) and inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using ELISA kits. Results showed that TBBPA induced oxidative stress, and activated the ROS-PI3K/AKT-NF-κB pathway, thereby resulting in inflammatory responses. TBBPA upregulated apoptosis-related genes (Caspase-3, Bax, and Bcl-2) and induced apoptosis. TBBPA upregulated the expression of RIPK3/MLKL, thereby exacerbating necroptosis. TPs intervention significantly mitigated these effects by reducing ROS, suppressing NF-κB activation, and restoring antioxidant enzyme activities (SOD, CAT). Moreover, TPs attenuated apoptosis and necrosis in the carp kidney, thereby enhancing the survival ability and immunity of common carp. Full article

Transcription factors play crucial roles in regulating gene expression, and any dysregulation in their levels could be involved in cancer progression. The role of androgen receptors (AR) and zinc finger (ZNF) proteins in tumors, like prostate cancer (PC), remains poorly understood. Moreover, due to the multifaceted transcriptional behavior of ARs and ZNFs, their biological role in cancer progression may also depend on the interplay with micro-RNAs (miRNAs). Based on The Cancer Genome Atlas (TCGA) database, we analyzed the expression levels of zinc finger transcripts and ARs in PC. Specifically, exploring their involvement in cancer progression and regulation by miRNAs. The analysis relied on several tools to create a multivariate combination of the original biomarkers to improve their diagnostic efficacy. Multidimensional Scaling (MDS) identified two new dimensions that were entered into a regression analysis to determine the best predictors of overall survival (OS) and disease-free interval (DFI). A combination of both dimensions predicted almost 50% (R² = 0.46) of the original variance of OS. Kaplan–Meier survival analysis also confirmed the significance of these two dimensions regarding the clinical output. This study showed preliminary evidence that several transcription factor expression levels belonging to the zinc family and related miRNAs can effectively predict patients’ overall PC survivability. Full article

Nuclear receptors are involved in multiple biological processes, among which RORγ can regulate the expression of inflammation-related genes and is thus frequently used as a therapeutic target for cancer. Canine mammary cancer is one of the most common tumor diseases in dogs, with a relative incidence rate of 46.71% for CMT in China over the past five years, severely threatening the life and health of dogs. Therefore, the search for novel drugs targeting canine mammary cancer is of great significance. This study aims to investigate how the RORγ inhibitors W6134 and XY018 affect the expression of inflammatory genes through histone modifications in CMT-N7 cells. These results show that W6134 and XY018 can upregulate signaling pathways related to inflammation and apoptosis and influence the expression of associated genes. The close link between RORγ and inflammation-related genes further confirms that RORγ may serve as a therapeutic target for canine cancer. Additionally, ChIP-qPCR was used to detect the enrichment of histone markers such as P300, H3K27ac, H3K4me1, H3K9la, and H3K9bhb at the target loci of CXCL10 and MECOM genes. Collectively, our findings provide molecular evidence for the protective role of RORγ in canine mammary cancer, potentially by regulating inflammatory pathways via histone modifications, offering new insights for improving the cure rate and survival of affected dogs. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Heat stress transcription factor (Hsf) families play important roles in abiotic stress responses. However, previous studies reported that HsfBs genes may play diverse roles in response to heat stress. Here, we conducted functional analysis on a woodland strawberry Class B Hsf gene, FvHsfB1a, to improve thermotolerance. The structure of FvHsfB1a contains a typical Hsf domain for DNA binding at the N-terminus, and FvHsfB1a belongs to the B1 family of Hsfs. The FvHsfB1a protein was localized in the nucleus. The FvHsfB1a gene was expressed in various strawberry tissues and highly induced by heat treatment. Under heat stress conditions, ectopic expression of FvHsfB1a in Arabidopsis improves thermotolerance, with higher germination and survival rates, a longer primary root length, higher proline and chlorophyll contents, lower malonaldehyde (MDA) and O²⁻ contents, better enzyme activities, and greater expression of heat-responsive and stress-related genes compared to WT. FvWRKY75 activates the promoter of the FvHsfB1a gene through recognizing the W-box element. Similarly, FvWRKY75-OE lines also displayed a heat-tolerant phenotype, exhibiting more proline and chlorophyll contents, lower MDA and O²⁻ contents, and higher enzyme activities under heat stress. Taken together, our study indicates that FvHsfB1a is a positive regulator of heat stress. Full article

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML. Full article

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

This research examined the impact of dietary supplementation with Phlogacanthus pulcherrimus extract (PPE) on the growth, disease resistance, and expression of immune-, growth-, and antioxidant-related genes in Labeo chrysophekadion. Over 150 days, 90 fish from each group were fed diets with 0 (control), 0.25, 0.50, or 0.75 g/kg of PPE. Phytochemical analysis revealed phenolics (96.00 mg GAE/g), flavonoids (17.55 mg QE/g), anthraquinones, and triterpenoids, along with moderate antioxidant activity (IC₅₀ = 1314.08 μg/mL). One-way ANOVA of growth indices, including weight gain, specific growth rate, feed conversion ratio, and survival rate, revealed no significant differences (p > 0.05); however, PPE supplementation significantly enhanced immune and antioxidant gene expression. IL-1β was significantly (p < 0.05) upregulated at all doses, with the highest expression observed at 0.50 g/kg, showing a fivefold increase compared to the control. In addition, the highest relative expressions of IGF-1 and CAT were found at 0.75 g/kg, with 4.5-fold and 3.5-fold increases compared to the control, respectively. PPE at 0.75 g/kg decreased the cumulative mortality rate (CMR) by 20% compared to the control group, which had a CMR of 50% following exposure to Aeromonas hydrophila. PPE acted as an effective immunostimulant and antioxidant, supporting reduced antibiotic reliance in aquaculture. Full article

Members of the heat shock protein 20 (HSP20) family of proteins play an important role in responding to various forms of stress. Here, the expression of ClaHSP17.4 was induced by heat stress in watermelon. Then, a floral dipping approach was used to introduce the pCAMBIA1391b-GFP overexpression vector encoding the heat tolerance-related gene ClaHSP17.4 from watermelon into Arabidopsis thaliana, and we obtained ClaHSP17.4-overexpressing Arabidopsis plants. Under normal conditions, the phenotypes of transgenic and wild-type (WT) Arabidopsis plants were largely similar. Following exposure to heat stress, however, the germination rates (96%) of transgenic Arabidopsis plants at the germination stages were significantly higher than those of wild-type idopsis (17%). Specifically, the malondialdehyde (MDA) content of transgenic Arabidopsis was half that of the control group, while the activities of peroxidase (POD) and superoxide dismutase (SOD) were 1.25 times those of the control group after exposure to high temperatures for 12 h at the seedling stages. The proline content in ClaHSP17.4-overexpressing transgenic Arabidopsis increased by 17% compared to WT plants (* p < 0.05), while the soluble sugar content rose by 37% (* p < 0.05). These results suggest that ClaHSP17.4 overexpression indirectly improves the antioxidant capacity and osmotic regulatory capacity of Arabidopsis seedlings, leading to improved survival and greater heat tolerance. Meanwhile, the results of this study provide a reference for further research on the function of the ClHSP17.4 gene and lay a foundation for breeding heat-tolerant watermelon varieties and advancing our understanding of plant adaptation to environmental stress. Full article

Enhanced colony nutrition can support brood development, resulting in better physiological conditions and increased resilience in adult honey bees, particularly under stress. This study investigated the effects of colony nutrition and adult dietary supplementation with green propolis on bee health under fungicide exposure. Colonies were managed under food restriction or nutritional supplementation for 22 weeks. Newly emerged bees from each colony were then caged and fed protein diets consisting of honey-pollen patties contaminated or not with fungicide, and sucrose sugar syrup with or without aqueous green propolis extract. Bees from supplemented colonies showed greater body weight, higher hemolymph protein levels, and higher consumption of protein food after seven days in cages. Fungicide exposure reduced hemolymph protein levels, altered the expression of detoxification and immune-related genes, and significantly decreased bee survival. Interestingly, propolis supplementation alone changed gene expression patterns and slightly reduced longevity compared to bees not exposed to propolis or fungicide. However, under fungicide stress, bees that ingested propolis survived longer, indicating a protective effect. While colony nutritional supplementation clearly promotes honey bee resilience against fungicide exposure, feeding propolis also showed promising effects, though further studies are needed to determine an optimal dietary concentration. Full article

Soil salinity adversely affects crop growth and development, leading to reduced soil fertility and agricultural productivity. The indigenous salt-tolerant plant growth-promoting rhizobacteria (PGPR), as a sustainable microbial resource, do not only promote growth and alleviate salt stress, but also improve the soil microecology of crops. The strain H5 isolated from saline-alkali soil in Bachu of Xinjiang was studied through whole-genome analysis, functional annotation, and plant growth-promoting, salt-tolerant trait gene analysis. Phylogenetic tree analysis and 16S rDNA sequencing confirmed its classification within the genus Halomonas. Functional annotation revealed that the H5 genome harbored multiple functional gene clusters associated with plant growth promotion and salt tolerance, which were critically involved in key biological processes such as bacterial survival, nutrient acquisition, environmental adaptation, and plant growth promotion. The pot experiment under moderate salt stress demonstrated that seed inoculation with Halomonas sp. H5 not only significantly improved the agronomic traits of tomato seedlings, but also increased plant antioxidant enzyme activities under salt stress. Additionally, soil analysis revealed H5 treatment significantly decreased the total salt (9.33%) and electrical conductivity (8.09%), while significantly improving organic matter content (11.19%) and total nitrogen content (10.81%), respectively (p < 0.05). Inoculation of strain H5 induced taxonomic and functional shifts in the rhizosphere microbial community, increasing the relative abundance of microorganisms associated with plant growth-promoting and carbon and nitrogen cycles, and reduced the relative abundance of the genera Alternaria (15.14%) and Fusarium (9.76%), which are closely related to tomato diseases (p < 0.05). Overall, this strain exhibits significant potential in alleviating abiotic stress, enhancing growth, improving disease resistance, and optimizing soil microecological conditions in tomato plants. These results provide a valuable microbial resource for saline soil remediation and utilization. Full article

Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article

Background: Acute myeloid leukemia (AML) is a common and aggressive adults hematological malignancies. This study explored megakaryocyte–erythroid progenitors (MEPs) signature genes and constructed a prognostic model. Methods: Uniform manifold approximation and projection (UMAP) identified distinct cell types, with differential analysis between AML-MEP and normal MEP groups. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression selected biomarkers to build a risk model and nomogram for 1-, 3-, and 5-year survival prediction. Results: Ten differentially expressed genes (DEGs) related to overall survival (OS), six (AHSP, MYB, VCL, PIM1, CDK6, as well as SNHG3) were retained post-LASSO. The model exhibited excellent efficiency (the area under the curve values: 0.788, 0.77, and 0.847). Pseudotime analysis of UMAP-defined subpopulations revealed that MYB and CDK6 exert stage-specific regulatory effects during MEP differentiation, with MYB involved in early commitment and CDK6 in terminal maturation. Finally, although VCL, PIM1, CDK6, and SNHG3 showed significant associations with AML survival and prognosis, they failed to exhibit pathological differential expression in quantitative real-time polymerase chain reaction (qRT-PCR) experimental validations. In contrast, the downregulation of AHSP and upregulation of MYB in AML samples were consistently validated by both qRT-PCR and Western blotting, showing the consistency between the transcriptional level changes and protein expression of these two genes (p < 0.05). Conclusions: In summary, the integration of single-cell/transcriptome analysis with targeted expression validation using clinical samples reveals that the combined AHSP-MYB signature effectively identifies high-risk MEP-AML patients, who may benefit from early intensive therapy or targeted interventions. Full article

Hemolin has been identified as a crucial immune gene in insect immune defense. The silkworm is susceptible to infections by pathogenic microorganisms when reared on artificial diets. In this study, through comparative analysis of the expression patterns of BmHemolin in silkworms fed on mulberry leaves and artificial diets, we found that the expression of BmHemolin was significantly upregulated in silkworms reared on artificial diets, and this upregulation was highly likely induced by pathogenic microorganisms. Further interaction analysis revealed that BmHemolin could bind to pathogenic microorganisms and form aggregates. Meanwhile, BmHemolin enhanced the melanization and aggregation of hemocytes. Subsequent in vitro antibacterial experiments showed that BmHemolin had the ability to inhibit the growth of Escherichia coli. In vivo clearance experiments demonstrated that BmHemolin facilitated the clearance of pathogens in the body. Moreover, CRISPR/Cas9-mediated knockout of the BmHemolin gene led to the downregulation of antimicrobial peptides and phagocytosis-related factors, while an excess of BmHemolin could enhance the expression of these genes, thereby improving the silkworm’s immune resistance to Enterococcus mundtii and increasing survival rates. In summary, our research demonstrates that BmHemolin played a pivotal role in both humoral and cellular immunity in the silkworm, thereby defending against pathogen invasion. Full article