Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematopoietic malignancy, necessitating the exploration of innovative therapeutic approaches. Targeting epigenetic mechanisms has emerged as a promising avenue for cancer treatment. EP300 belongs to the KAT3 family of histone/non-histone lysine acetyltransferases, regulating gene expression by acetylating H3K27. However, the role of EP300 and its potential as a targeted therapy in DLBCL remains unknown.

The prevalence of depression in women is approximately twice that in men. Differences in androgens levels between men and women, due to gonadal differences, may be associated with the development of depression, although the underlying mechanisms are not well understood.

Chromium (Cr) contamination poses food safety and environmental challenges, yet the early-stage physiological and molecular responses to Cr(III) stress remain unclear. Citrus and tomato are economically important crops representing woody and herbaceous species, making them valuable models for studying heavy metal toxicity in plants. This study investigates the impact of Cr (III) exposure on citrus and tomato seedlings, with a focus on physiological phenotypes and transcriptional response. Citrus seed germination declines with increasing Cr(III) concentrations, while low Cr(III) levels promote tomato germination, with inhibition occurring above 1 g/L. Under hydroponic conditions, Cr (III) severely hampers root and leaf growth in both citrus and tomato plants, accompanied by decreased net photosynthetic rate. Using a GFP-based confocal microscopy system, we observed reduced fluorescence intensity within three days of Cr(III) exposure (100 mg/L and 500 mg/L), indicating early cellular damage. Biochemical assays revealed oxidative stress, marked by increased H2O2, malondialdehyde (MDA), and antioxidant enzyme activity. Additionally, low Cr (III) concentrations could result in the death of various microorganisms, including Escherichia coli, Agrobacterium rhizogenes, and Agrobacterium tumefaciens. Transcriptomic analysis identified differentially expressed genes related to "MAPK signaling pathway" and "Plant hormone signal transduction pathway". Transcription of many transcription factors, such as bHLH, WRKY, and MYB, also underwent significant changes.

Long-term exposure to arsenic (As), which is a ubiquitous environmental contaminant, significantly enhances the risk of multiple cancers, including bladder and lung cancers. In recent years, the important roles of circular RNAs (circRNAs) in tumorigenesis and development have attracted widespread attention. However, the specific molecular mechanisms by which circRNAs promote bladder cancer development following exposure to arsenic remain incompletely understood. This study is the first to demonstrate that circPDE3B is significantly upregulated in a cell model of transformation triggered by arsenic and that it promotes this transformation process. Our study elucidated the biological function of circPDE3B in vitro, in SV-HUC-1 cells, showing that it accelerates the malignant transformation from arsenic via increasing cell proliferation and inhibiting apoptosis. Furthermore, we delineated a novel molecular mechanism whereby circPDE3B directly binds to NF-κB and STAT3, inhibiting their ubiquitination and increasing their stability. This, in turn, affects downstream HIF-1α expression, promoting the malignant transformation of SV-HUC-1 cells and eventually resulting in bladder carcinogenesis. Our research reveals the critical regulatory role of circPDE3B in the arsenic-triggered malignant transformation within SV-HUC-1 cells. This study offers broader perspectives on the molecular mechanisms driving bladder cancer progression, while also identifying potential targets for early diagnosis and treatment of bladder tumour.

Bacteria have been known to thrive in challenging environmental niches through diverse phenomena. Swarming is one such favourable adaptations that could help bacteria survive extreme conditions. Therefore, targeting swarming is crucial for improving our understanding of bacterial motility and preventing related infections. Bacillus cereus, which causes food poisoning, has been shown to perform swarming, and salts like NaCl can act as a food preservative to control bacterial growth. To explore the possible alterations in the swarming of Bacillus cereus in the presence of salt, the present study encompasses the effect of NaCl on the swarming characteristics of a natural bacterial isolate, Bacillus cereus MHS, with a hyperswarming phenotype. Here we report that increased NaCl in growth media could induce a reduction in swarming motility and pattern of MHS on Luria agar plates. This observed reduction in swarming was found to be associated with reduced flagellation and a reduction in the abundance of bacterial nanotubes. Gene expression studies supported the phenotypic and ultrastructure observations as the expressions of bfla and ymdB genes, involved in formations of flagella and nanotubes, respectively, were found to be reduced in the swarming MHS cells in the presence of increased NaCl. It was also observed that the salt-induced reduction in swarming of MHS is associated with the reduced expression of the quorum sensing regulator gene plcR. This study first time reports the bacterial nanotubes in a Bacillus cereus strain indicating a possible link between the bacterial nanotube formation and hyperswarming phenotype in Bacillus cereus MHS.

This study aimed to investigate the target genes of active components in Dingxiang Guanshitong (DGST) and evaluate their significance in the prognosis of esophageal cancer (EC) through integrated approaches, including network pharmacology, molecular docking, prognostic analysis, and in vitro experiments. EC-related data were obtained from TCGA database, while SymMap and TCMSP databases were utilized to identify DGST's bioactive components and their targets. A comprehensive network was constructed to map component-target-pathway interactions. Bioinformatics analysis revealed 113 key signaling pathways and 424 differentially expressed targets associated with DGST and EC. Univariate Cox regression analysis identified 21 target genes significantly correlated with overall survival (OS) in EC patients, among which six exhibited pharmacological activity. Molecular docking confirmed strong binding affinities between DGST's active components and critical targets. In vitro experiments demonstrated that DGST suppressed migration, invasion, and proliferation of TE-1 and EC-109 cell lines while promoting apoptosis. Furthermore, DGST significantly upregulated the protein and mRNA expression of the prognostic factor NFKBIA, while downregulating GPER1, HK2, MAOB, TNFRSF10B, and ECE1. This study is the first to elucidate the molecular mechanisms underlying DGST's anti-EC effects. DGST exerts its anti-cancer activity by targeting prognosis-related genes and modulating the expression of critical molecular markers, thereby inhibiting EC progression and improving therapeutic outcomes. These findings provide a robust scientific foundation for the clinical application of DGST and further exploration of its mechanistic basis.

Localized ablative immunotherapy (LAIT), a combination of photothermal therapy (PTT) and the immunostimulant glycated chitosan (GC), has demonstrated therapeutic efficacy in cancer treatment. However, its impact on the tumor microenvironment (TME), particularly on tumor-infiltrating natural killer (TINK) cells, remains to be fully elucidated. Using single-cell RNA sequencing (scRNAseq), we analyzed the transcriptional and functional modulations of TINK cells by LAIT in a mouse breast cancer model. Additionally, we investigated immune checkpoint inhibitor (ICI)-induced changes in NK cells across multiple cancer types and evaluated the clinical relevance of these transcriptional changes using The Cancer Genome Atlas (TCGA) database. ScRNAseq revealed five NK cell subtypes, with LAIT increasing the proportion of interferon-enriched NK cells and enhancing NK cell differentiation and cytotoxicity. Functional analyses demonstrated that LAIT upregulated activation, cytotoxic, and interferon pathway genes while downregulating immune-suppressive genes, effects largely driven by GC. Comparative analysis showed significant transcriptional overlap between ICI and LAIT, highlighting shared pathways in NK cell-mediated cytotoxicity and chemokine signaling. Prognostic models constructed from ICI- and LAIT-induced gene signatures effectively stratified breast cancer patients by survival risk, with LAIT-induced genes showing the highest predictive performance. Furthermore, higher NK cell proportions and the expression of key prognostic genes, such as PSME2, IGKC, and KLRB1, were associated with improved overall survival. LAIT and ICIs enhance NK cell-mediated antitumor responses via distinct yet complementary mechanisms, emphasizing their potential for synergistic use. These findings provide novel insights into NK cell modulation within the TME and support the development of combinatorial immunotherapy strategies.

Prediabetes, also known as impaired glucose tolerance (IGT), is a common metabolic disorder and is often considered a risk factor for the development of diabetes. Metformin (MET) is a widely used medication for the treatment of diabetes and has the potential to improve insulin sensitivity and blood sugar control. This work aimed to investigate the impact of MET treatment on serum miRNA expression in IGT patients and explore the quantitative changes in miRNA after MET treatment.

Thiamine, also known as vitamin B1, serves as an inducer that strengthens plants and elicits defense responses to enhance resistance against pathogens. Currently, the antiviral mechanism of thiamine remains unclear. Here, we used maize chlorotic mottle virus (MCMV) as a model to elucidate the antiviral mechanism of thiamine. We found that thiamine application improved maize resistance to the MCMV. Transcriptome sequencing indicated that MCMV infection influenced the expression of thiamine synthesis pathway-related genes. Besides, MCMV P31 interacted with the key thiamine synthesis factor, ZmTHIC in cytoplasm, and blocked ZmTHIC entering into chloroplast. Using the cucumber mosaic virus (CMV) induced gene silencing system, we silenced ZmTHIC in maize, resulting in higher accumulation of MCMV compared to the control plants. LC-MS analysis revealed that both ZmTHIC silencing and MCMV infection reduced the thiamine content in maize. Thiamine treatment prior to MCMV infection enhanced plant defense responses by activating the MAPK pathway and promoting lignin synthesis in plant cell walls, ultimately inhibiting MCMV infection. Taking together, our results suggest that thiamine induced the synthesis of lignin and MAPK pathway to enhance the systemic immunity, promoting antiviral defense in maize. MCMV P31 hijacked ZmTHIC and prevented it from entering the chloroplasts, thereby inhibiting the synthesis of thiamine to dampen the synthesis of lignin and MAPK pathway to dampen the plant immunity. This research provides new insights into the antiviral mechanism of thiamine.

Nasopharyngeal carcinoma (NPC) is a unique cancer type originating from the nasopharynx. To investigate novel strategies for improving prognosis and reducing the adverse effects of current treatments, this study examined the efficacy of hellebrigenin. Hellebrigenin demonstrated selective cytotoxicity against NPC-BM and NPC-039 cell lines without harming normal nasopharyngeal cells. Treatment with hellebrigenin resulted in G2/M cell cycle arrest in both NPC cell lines. The apoptotic phenomena induced by hellebrigenin included chromatin condensation, increased apoptotic cells and altered mitochondrial membrane potential. Proteomics analysis and the bioinformatic data identified coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) as a candidate oncogene in NPC. Moreover, the combination of CHCHD2 siRNA, CHCHD2 plasmid and hellebrigenin pointed out that CHCHD2 could be a critical mediator of hellebrigenin-induced apoptosis. The combined treatment of hellebrigenin with mitogen-activated protein kinase inhibitors revealed the involvement of the extracellular signal-regulated kinases and c-Jun N-terminal kinases pathways in hellebrigenin-induced apoptosis in NPC cells. In vivo studies demonstrated that hellebrigenin suppressed the tumour volume without affecting body weight, accompanied by the downregulation of Ki67 and CHCHD2 expression. In conclusion, this study provides evidence that hellebrigenin induces NPC apoptosis through regulating CHCHD2 both in vitro and in vivo.

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces demethylation at DNMT3B regulatory elements including a candidate enhancer located ∼10 kb upstream of the DNMT3B transcription start site, as well as at the promoter of TERT (telomerase reverse transcriptase), a potential activator of DNMT3B expression. These demethylation events correlate with upregulation of DNMT3B expression. These findings suggest that combining inhibitors targeting DNMT1, the maintenance methyltransferase, with those targeting DNMT3A/3B, the de novo methyltransferases, or using pan-DNMT inhibitors, could enhance anticancer efficacy and reduce resistance.

Ischemic stroke (IS) is one of the most sinister diseases and the second leading cause of death in the world. Eugenol (EUG) is a natural and biologically active component that can be extracted from various plants. Studies have found that EUG can alleviate middle cerebral artery occlusion and reperfusion (MCAO/R) injury in mice, but the specific mechanism remains vague. Tripartite motif protein 59 (TRIM59) is a member of TRIM protein family, a group of E3 ubiquitin ligases. In this article, we conducted both in vivo and in vitro experiments to determine the effect of EUG on ischemia-reperfusion injury and to explore the underlying mechanisms by manipulating the expression of TRIM59. Results showed that EUG alleviates acute injury and promotes functional repair of mouse IS by enhancing the phagocytosis of microglia through up-regulating the TRIM59, activating the STAT3 pathway and promoting the expression of CD11b.

A cutting-edge smart nano-hybrid technology, offering potential benefits for plants, has recently been developed to address the pervasive issue of heavy metal pollution. This study explored the potential of this technology in mitigating chromium (Cr) stress in rapeseed using a nano-based system that integrates 100 μM hydrogen sulphide (H2S) and 50 μM manganese nanoparticles (Mn-NPs). This strategy reveals Cr-stress tolerance mechanisms through physiological assessments and transcriptome data analysis. The results demonstrated that Cr stress substantially inhibited rapeseed growth while increasing oxidative damage markers (MDA and ROS levels). Conversely, Mn-NP and H2S co-treatment significantly mitigated these effects, as shown by: (1) restored growth metrics, (2) improved photosynthetic performance and membrane integrity, (3) optimized Mn/H2S homeostasis, and (4) reduced tissue Cr accumulation. The reduction in Cr content was attributed to enhanced Cr-detoxification mechanisms, driven by the upregulation of enzymatic antioxidant activities, like superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase. Transcriptomic profiling revealed marked upregulation of genes involved in core metabolic processes, including photosynthetic pathways, carbon assimilation, secondary metabolite biosynthesis, inositol/phosphatidylinositol signalling systems, and stress-response networks. Under Cr stress, Mn-NP and H2S co-treated rapeseed plants displayed enhanced tolerance, highlighting the crucial role of these signalling agents in activating Cr-defence mechanisms. Our findings demonstrate that the integration of nanotechnology and gasotransmitter signalling molecule H2S presents a novel strategy for enhancing heavy metal tolerance and plant productivity in contaminated soils.

Kujigamberol, a dinorlabdane compound isolated from Kuji amber, exerts multiple biological effects, including anti-allergic and anti-inflammatory activities. The present study demonstrated that kujigamberol inhibited cytokine production by T cells. In response to a phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM) stimulation, kujigamberol suppressed interferon-γ (IFN-γ) and interleukin-2 (IL-2) mRNA expression in murine T-cell lymphoma BW5147 cells stably transfected with the T-box transcription factor eomesodermin. IL-4 and Fas ligand mRNA expression was also inhibited by kujigamberol. In the murine cytotoxic T-cell line CTLL-2, kujigamberol more strongly decreased IFN-γ mRNA expression induced by IM alone than that induced by the combination of PMA and IM. A luciferase reporter assay showed that kujigamberol preferentially reduced nuclear factor of activated T cell (NFAT)-dependent transcription in human embryonic kidney 293T cells. Unlike the calcineurin inhibitor FK506, kujigamberol did not markedly affect NFATc2 protein levels in BW5147 cells but interfered with the binding of NFATc2 to the IFN-γ and IL-2 promoters. These results indicate that kujigamberol inhibited IFN-γ and IL-2 mRNA expression by preventing the binding of NFATc2 to their promoters; therefore, it has potential as an immunosuppressive agent.

Curcumin, a major phytochemical derived from Curcuma longa, has been shown to enhance the efficacy of chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and cisplatin by overcoming drug resistance, making it a promising adjunct in the treatment of glioblastoma. However, the global gene-expression changes triggered by curcumin in glioblastoma remain underexplored. In this study, we investigated the effects of curcumin on human glioblastoma (U87 MG) cells, where it significantly reduced cell viability and proliferation in a dose- and time-dependent manner and induced apoptosis without affecting senescence. Transcriptomic analysis revealed 5036 differentially expressed genes, with pathway enrichment identifying 13 dysregulated cancer-associated pathways. Notably, curcumin modulated several key regulators involved in MAPK, Ras, TGF-β, Wnt, Cytokine, and TNF signaling pathways. Several apoptosis and cell cycle-associated genes, including PRKCG, GDF7, GDF9, GDF15, GDF5, FZD1, FZD2, FZD8, AIFM3, TP53AIP1, CRD14, NIBAN3, BOK, BCL2L10, BCL2L14, BNIPL, FASLG, GZMM, TNFSF10, TNFSF11, and TNFSF4, were significantly altered. Several pro-apoptotic and anti-BCL, cell-cycle-regulated genes were modulated following curcumin treatment, emphasizing its potential role in curcumin-mediated anti-tumor effects. This study provides insight into the molecular mechanisms underlying curcumin's action against glioblastoma.

Epigenetic dysregulation has emerged as an important player in the pathobiology of neurodegenerative diseases (NDDs), such as Alzheimer's, Parkinson's, and Huntington's diseases. Aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs have been shown to contribute to neuronal dysfunction and degeneration. These alterations are often exacerbated by environmental toxins, which induce oxidative stress, inflammation, and genomic instability. Reversing epigenetic aberrations may offer an avenue for restoring brain mechanisms and mitigating neurodegeneration. Herein, we revisit the evidence suggesting the ameliorative effects of epigenetic modulators in toxin-induced models of NDDs. The restoration of normal gene expressions, the improvement of neuronal function, and the reduction in pathological markers by histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors have been demonstrated in preclinical models of NDDs. Encouragingly, in clinical trials of Alzheimer's disease (AD), HDAC inhibitors have caused improvements in cognition and memory. Combining these beneficial effects of epigenetic modulators with neuroprotective agents and the clearance of misfolded amyloid proteins may offer synergistic benefits. Reinforced by the emerging methods for more effective and brain-specific delivery, reversibility, and safety considerations, epigenetic modulators are anticipated to minimize systemic toxicity and yield more favorable outcomes in NDDs. In summary, although still in their infancy, epigenetic modulators offer an integrated strategy to address the multifactorial nature of NDDs, altering their therapeutic landscape.

Tumor angiogenesis and metastasis are critical processes in the progression of colon carcinoma. Curcumol, a bioactive sesquiterpenoid derived from curcuma, exhibits anti-angiogenic properties, though its underlying mechanisms remain unclear. In this study, an HT-29 xenograft mouse model demonstrated that curcumol combined with oxaliplatin significantly suppressed tumor growth (Ki67↓) and microvessel density (CD31↓). In vitro assays revealed that curcumol dose dependently inhibited proliferation (MTT), migration (Transwell), and tube formation (CAM assay) in Caco-2/HT-29 and HUVEC cells. Mechanistically, curcumol downregulated OTUB1 expression, promoting TGFB1 degradation via the ubiquitin-proteasome pathway. OTUB1 overexpression activated the TGFB1/VEGF axis, enhancing cell invasiveness and angiogenesis-effects reversed by high-dose curcumol. These findings identify the OTUB1-TGFB1/VEGF axis as a key target of curcumol in inhibiting colon cancer angiogenesis, elucidating its anti-tumor mechanism and offering a novel therapeutic strategy for targeted treatment.

The composition of genomic mediators of glucocorticoid actions in the brain remains elusive because of low-statistical-power experiments and the associated transcriptomic data with very low consistency. The problem is further exaggerated by the underrepresentation of chronic experiments and the interpretation of differentially expressed genes without understanding their contribution to the total transcriptomic activity. To fill existing gaps in knowledge, we have performed a large transcriptomic experiment, testing the effects of prolonged treatment with corticosterone on the hippocampal transcriptome (RNA sequencing). The experiment showed that prolonged treatment with corticosterone induced a set of transcriptomic effects that were replicable across treatment durations, including genes relevant for human PTSD (Opalin, Pllp, Ttyh2, Lpar1) and prolonged stress in animals (Cnp, Fam163a, Fcrls, Tmem125). Some of the affected genes are specific for oligodendrocytes, neurons, astrocytes, immune cells, the vascular system, and brain ventricles, indicating that glucocorticoids may affect all central nervous system components. The data also showed that the largest changes in expression of corticosterone-responsive genes are restricted to genes with a relatively low expression level and small contribution to the overall pool of mRNAs in the hippocampus. As a result, even a large change in the number of affected genes leads to a small change in the number of newly synthesized mRNA copies. This means, in turn, that the transcriptomic changes induced by corticosterone have low-cost effects on the brain. This specificity of transcriptomic responses also poses a challenge for the interpretation of data and constitutes a potential source of reporting bias in past studies. Therefore, there is a need for further research on products of gene expression, both at the transcriptomic and proteomic levels, during stress conditions.

Aluminum toxicity severely inhibits root elongation and nutrient uptake, causing global agricultural yield losses. Dissolved Al3+ are accumulating in plants and subsequently entering food chains via crops and forage plants. Chronic dietary exposure to Al3+ poses a risk to human health. In this study, Pseudomonas sp. strain ADAl3-4, isolated from plant rhizosphere soil, significantly enhanced plant development and biomass. Phenotypic validation using Arabidopsis mutants showed that strain ADAl3-4 regulates plant growth and development under aluminum stress by reprogramming the cell cycle, regulating auxin and ion homeostasis, and enhancing the root absorption of Al3+ from the soil. Transcriptomic and biochemical analyses showed that strain ADAl3-4 promotes plant growth via regulating signal transduction, phytohormone biosynthesis, flavonoid biosynthesis, and antioxidant capacity, etc., under aluminum stress. Our findings indicate that Pseudomonas sp. strain ADAl3-4 enhances plant development and stress resilience under Al3+ toxicity through a coordinated multi-dimensional regulatory network. Furthermore, strain ADAl3-4 promoted the root absorption of aluminum rather than the transportation of Al to the aerial part, endowing it with application prospects.

Lymphoma is one of the malignant tumors that significantly threatens human health. Quadrigemine I, an indole alkaloid derived from the leaves of Psychotria pilifera, has been studied for its potential anti-tumor properties, but its mechanisms remain poorly understood. The CCK-8 assay was used to determine the cytotoxic effect of quadrigemine I on lymphoma cells. Flow cytometry was employed to analyze apoptosis and reactive oxygen species (ROS) levels in these cells. DNA damage was assessed by the comet assay, and the underlying mechanisms were investigated using RNA sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR). The anti-tumor activity of quadrigemine I was evaluated in tumor xenograft mice. Quadrigemine I suppressed lymphoma cell proliferation with an IC50 of 0.46 µM. It induced apoptosis, promoted ROS generation, and caused DNA damage in tumor cells. RNA-seq analysis revealed that the significantly differentially expressed genes were notably enriched in the ErbB, p53, and apoptosis signaling pathways. RT-qPCR demonstrated altered expression levels of key genes in the aforementioned pathways. In vivo, quadrigemine I significantly inhibited tumor growth in xenograft mice by increasing apoptosis in tumor tissues, with reduced Ki-67 and Bcl-2 expression and elevated cleaved caspase-3 levels. Quadrigemine I may serve as a novel anti-tumor agent for lymphoma therapy.