Search Results (39)

Melanoma remains a highly aggressive malignancy, particularly in advanced metastatic stages where therapeutic options are limited. Natural compounds provide a structural basis for discovering novel anticancer agents. In this study, we employed an integrated in silico approach to evaluate the pharmacokinetic properties, toxicity profiles, and molecular targets of key alkaloids from Chelidonium majus, including berberine, sanguinarine, chelerythrine, chelidonine, protopine, umbelliferone and coptisine. ADME/T predictions (SwissADME and DeepPK) revealed favorable drug-likeness and oral bioavailability for most compounds, with berberine exhibiting the most balanced safety and absorption profile. All compounds demonstrated high intestinal absorption (>99%) and implicated key melanoma targets, including APE1/Ref-1, CXCR4, CCR2, TLR8, galectin-3, and VEGFR2. These molecules represent valuable templates for the development of melanoma therapies. Among the tested compounds, chelidonine emerged as a potential APE1 inhibitor, exhibiting the highest binding affinity and forming specific interactions within the enzyme’s catalytic site, suggesting its potential as a DNA repair-targeted agent in melanoma. These findings support the further exploration of natural alkaloids, including structural optimization or advanced formulation strategies, to enhance safety, bioavailability, and therapeutic efficacy in melanoma. Full article

Fig (Ficus carica L.), a deciduous fruit tree that belongs to the Moraceae family, is cultivated worldwide as an important fruit crop for raw and processed foods. Quantitative real-time PCR (RT-qPCR) is a widely used method in F. carica to elucidate expression of genes related to various physiological responses. However, no studies have identified appropriate reference genes for RT-qPCR normalization in F. carica. In this study, 12 genes were selected from the F. carica genome as candidate reference genes for normalizing target gene expression. All candidate genes exhibited high amplification efficiency and specificity in the absence of primer dimers or extra PCR amplicons. The expression levels of the candidate genes were measured in three different plant tissues (fruit, leaf, and stem) under fungal pathogen infection using RT-qPCR. Their expression stabilities were evaluated using four computational algorithms: geNorm, Normfinder, delta-Ct, and BestKeeper. The RefFinder program was also used to calculate the geometric mean of the stability rankings obtained from these algorithms. The comprehensive ranking revealed that FcYLS8, FcPP2A, and FcAP2M were the most stable reference genes under biotic stress in the fruits, leaves, and stems, respectively. In contrast, traditional reference genes such as FcACT2, FcEF-1α, FcGAPDH, FcUBC21, and FcUBQ5 exhibited relatively low expression stability in all tested tissues. This study identified and validated stable reference genes for RT-qPCR normalization in F. carica, thus providing a valuable resource for accurate gene expression studies under biotic stress and highlighting the importance of validating reference genes to ensure reliable and reproducible RT-qPCR analysis. Full article

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options due to the lack of estrogen, progesterone, and HER2 receptors. This study investigated the synergistic anticancer effects of recombinant human apurinic/apyrimidinic endonuclease 1/redox factor-1 (rhAPE1/Ref-1) and acetylsalicylic acid (ASA), a combination that has not been previously tested in vivo. Methods: We treated MDA-MB-231 TNBC cells with rhAPE1/Ref-1, ASA, or their combination to assess cell viability and apoptosis in vitro. In vivo, a murine xenograft model was established to evaluate the efficacy of the combination treatment on tumor growth, tumor-specific biomarkers, and key apoptotic proteins. The safety profile of the combination therapy was also assessed by monitoring hematological parameters. Results: While monotherapy with either rhAPE1/Ref-1 or ASA had minimal effects, their combination significantly reduced cell viability and enhanced apoptosis in vitro by increasing DNA fragmentation. These synergistic cytotoxic effects were significantly inhibited by the receptor for advanced glycation end-products (RAGE) siRNA, suggesting that RAGE acts as an important mediator. In the xenograft model, the combination treatment suppressed tumor growth by approximately 70%, an effect comparable to paclitaxel (PTX). This was confirmed by a significant reduction in the plasma levels of TNBC biomarkers (CEA, CA27-29, and CA15-3) and increased tumor apoptosis via the upregulation of p53 and Bax and downregulation of Bcl-2. Notably, ASA, alone or combined with rhAPE1/Ref-1, induced the expression of RAGE in MDA-MB-231 tumors. In contrast to PTX, the combination of rhAPE1/Ref-1 and ASA did not cause hematological toxicity, such as anemia or thrombocytopenia. Conclusions: The combination of rhAPE1/Ref-1 and ASA represents a promising new therapeutic strategy for TNBC by enhancing apoptosis and significantly inhibiting tumor progression in a mouse xenograft model. Full article

In modern livestock production, obtaining accurate body weight measurements for pigs is essential for feeding management and economic assessment, yet conventional weighing is laborious and can stress animals. To address these limitations, we developed a contactless image-based pipeline that first uses BiRefNet for high-precision background removal and YOLOv11-seg to extract the pig dorsal mask from top-view RGB images; from these masks we designed and extracted 17 representative phenotypic features (for example, dorsal area, convex hull area, major/minor axes, curvature metrics and Hu moments) and included camera height as a calibration input. We then compared eight machine-learning and deep-learning regressors to map features to body weight. The segmentation pipeline achieved mAP₅₀–₉₅ = 0.995 on the validation set, and the XGBoost regressor gave the best test performance (MAE = 3.9350 kg, RMSE = 5.2372 kg, R² = 0.9814). These results indicate the method provides accurate, low-cost and computationally efficient weight prediction from simple RGB images, supporting frequent, noninvasive monitoring and practical deployment in smart-farming settings. Full article

This study addresses challenges such as multi-scale defects, varying lighting, and irregular shapes by proposing an improved YOLOv10 model that integrates the ECA attention mechanism, RefConv feature enhancement module, and WIoU loss function for complex pavement defect detection. The RefConv dual-branch structure achieves feature complementarity between local details and global context (mAP increased by 2.1%), the ECA mechanism models channel relationships using 1D convolution (small-object recall rate increased by 27%), and the WIoU loss optimizes difficult sample regression through a dynamic weighting mechanism (location accuracy improved by 37%). Experiments show that on a dataset constructed from 23,949 high-resolution images, the improved model’s mAP reaches 68.2%, which is an increase of 6.2% compared to the baseline YOLOv10, maintaining a stable recall rate of 83.5% in highly reflective and low-light scenarios, with an inference speed of 158 FPS (RTX 4080), providing a high-precision real-time solution for intelligent road inspection. Full article

In response to the low precision of ore image segmentation under complex working conditions, an improved Mask R-CNN segmentation algorithm is proposed. The traditional Mask R-CNN uses a simple deconvolution operation to generate masks, which can lead to the loss of ore edge information and insufficient detail processing, affecting segmentation accuracy. Therefore, an improved model based on the Mask R-CNN framework is proposed in this paper. By introducing the Re-parameterized Refocus Convolution (RefConv) into the residual networks, the expressive power of the feature extraction network is enhanced. Meanwhile, the Efficient Channel Attention (ECA) is embedded in the output part of the Feature Pyramid Network (FPN), enhancing the model’s ability to capture key information. The improved Mask R-CNN network structure can reduce the loss of ore detail information caused by convolution operations and improve the network’s segmentation accuracy. Comparative experiments between the improved algorithm and the original algorithm show that the average Intersection over Union (MIoU) of the improved algorithm reached 92.8%, which is about a 6.8% increase compared to the original Mask R-CNN algorithm; the average pixel accuracy (mAP) is 97.2%, which is about a 5.1% increase compared to the original algorithm, indicating higher detection accuracy for ore identification and segmentation. Full article

To address the challenge posed by the abundance of small objects with weak object features and little information in the images of underwater biomonitoring scenarios, and the added difficulty of recognizing these objects due to light absorption and scattering in the underwater environment, this study proposes an improved RHS-YOLOv8 (Ref-Dilated-HBFPN-SOB-YOLOv8). Firstly, a combination of hybrid inflated convolution and RefConv is used to redesign the lightweight Ref-Dilated convolution block, which reduces the model computation. Second, a new feature pyramid network fusion module, the Hybrid Bridge Feature Pyramid Network (HBFPN), is designed to fuse the deep features with the high-level features, as well as the features of the current layer, to improve the feature extraction capability for fuzzy objects. Third, Efficient Localization Attention (ELA) is added to reduce the interference of irrelevant factors on prediction. Fourth, an Involution module is introduced to effectively capture spatial long-range relationships and improve recognition accuracy. Finally, a small object detection branch is incorporated into the original architecture to enhance the model’s performance in detecting small objects. Experiments based on the DUO dataset show that RHS-YOLOv8 reduces 9.95% of computing power, while mAP@0.5 and mAP@0.50:0.95 are improved by 2.54% and 4.31%, respectively. Compared with other cutting-edge underwater object detection algorithms, the present algorithm improves the detection accuracy while lightweighting the improvement, which effectively enhances the capability to detect small underwater objects. Full article

The rubber elongation factor (REF) is the most abundant protein in the latex of Hevea brasiliensis, which is closely related to natural rubber biosynthesis. In order to gain a deeper understanding of the transcriptional regulation mechanism of HbREF1, a 1758 bp genomic DNA fragment of the HbREF1 promoter was isolated. Promoter sequence analysis revealed several transcription factor binding sites in the HbREF1 promoter, such as bZIP, bHLH, EIL, AP2/ERF, MYB, and Trihelix. To assess the promoter activity, a series of HbREF1 promoter deletion derivatives were created and fused with firefly luciferase (LUC). The LUC image demonstrated that all of the HbREF1 promoters exhibited transcriptional activity. Furthermore, the assay revealed the presence of multiple regulatory elements within the promoter region that negatively regulate the transcriptional activity. Subsequent analysis of the transcriptional activity following treatment with phytohormones identified an ABA-responsive element located between −583 bp and −200 bp, an ET-responsive element between −718 bp and −583 bp, a JA-responsive element between −1758 bp and −1300 bp, and a SA-responsive element between −1300 bp and −718 bp. These results were largely consistent with the predictions of cis-acting elements. This study has established significant groundwork for future investigations into the regulatory mechanism of HbREF1. Full article

Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. The prevalence of IBD is increasing with approximately 4.9 million cases reported worldwide. Current therapies are limited due to the severity of side effects and long-term toxicity, therefore, the development of novel IBD treatments is necessitated. Recent findings support apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1) as a target in many pathological conditions, including inflammatory diseases, where APE1/Ref-1 regulation of crucial transcription factors impacts significant pathways. Thus, a potential target for a novel IBD therapy is the redox activity of the multifunctional protein APE1/Ref-1. This review elaborates on the status of conventional IBD treatments, the role of an APE1/Ref-1 in intestinal inflammation, and the potential of a small molecule inhibitor of APE1/Ref-1 redox activity to modulate inflammation, oxidative stress response, and enteric neuronal damage in IBD. Full article

Apurinic/apyrimidinic endonuclease 1 (APE1), also known as redox factor-1 (Ref-1), is a multifunctional protein that exists widely in living organisms. It can specifically recognize and cleave the DNA in apurinic/apyrimidinic (AP) sites in the base excision repair (BER) pathway, as well as regulate the expression of genes to activate some transcription factors. The abnormal expression and disruptions in the biological functions of APE1 are linked to a number of diseases, including inflammation, immunodeficiency, and cancer. Hence, it is extremely desired to monitor the activity of APE1, acquiring a thorough understanding of the healing process of damaged DNA and making clinical diagnoses. Thanks to the advent of DNA nanotechnology, some nanodevices are used to image the activity of APE1 with great sensitivity and simplicity. In this review, we will summarize developments in DNA-nanotechnology-empowered fluorescence imaging in recent years for APE1 activity according to different types of DNA probes, which are classified into linear DNA probes, composite DNA nanomaterials, and three-dimensional (3D) DNA nanostructures. We also highlight the future research directions in the field of APE1 activity imaging. Full article

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos-related primary oxidative damage is counteracted in the lungs by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet been fully understood. Moreover, asbestos exposure has been associated with induced EMT events, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells; as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Taken as a whole, these results show, for the first time, crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, thus improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer. Full article

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox regulation. The redox activity of APE1/Ref-1 is involved in inflammatory responses and regulation of DNA binding of transcription factors related to cell survival pathways. However, the effect of APE1/Ref-1 on adipogenic transcription factor regulation remains unknown. In this study, we investigated the effect of APE1/Ref-1 on the regulation of adipocyte differentiation in 3T3-L1 cells. During adipocyte differentiation, APE1/Ref-1 expression significantly decreased with the increased expression of adipogenic transcription factors such as CCAAT/enhancer binding protein (C/EBP)-α and peroxisome proliferator-activated receptor (PPAR)-γ, and the adipocyte differentiation marker adipocyte protein 2 (aP2) in a time-dependent manner. However, APE1/Ref-1 overexpression inhibited C/EBP-α, PPAR-γ, and aP2 expression, which was upregulated during adipocyte differentiation. In contrast, silencing APE1/Ref-1 or redox inhibition of APE1/Ref-1 using E3330 increased the mRNA and protein levels of C/EBP-α, PPAR-γ, and aP2 during adipocyte differentiation. These results suggest that APE1/Ref-1 inhibits adipocyte differentiation by regulating adipogenic transcription factors, suggesting that APE1/Ref-1 is a potential therapeutic target for regulating adipocyte differentiation. Full article

The APETALA2/Ethylene-Responsive Transcriptional Factors containing conservative AP2/ERF domains constituted a plant-specific transcription factor (TF) superfamily, called AP2/ERF. The configuration of the AP2/ERF superfamily in maize has remained unresolved. In this study, we identified the 229 AP2/ERF genes in the latest (B73 RefGen_v5) maize reference genome. Phylogenetic classification of the ZmAP2/ERF family members categorized it into five clades, including 27 AP2 (APETALA2), 5 RAV (Related to ABI3/VP), 89 DREB (dehydration responsive element binding), 105 ERF (ethylene responsive factors), and a soloist. The duplication events of the paralogous genes occurred from 1.724–25.855 MYA, a key route to maize evolution. Structural analysis reveals that they have more introns and few exons. The results showed that 32 ZmAP2/ERFs regulate biotic stresses, and 24 ZmAP2/ERFs are involved in responses towards abiotic stresses. Additionally, the expression analysis showed that DREB family members are involved in plant sex determination. The real-time quantitative expression profiling of ZmAP2/ERFs in the leaves of the maize inbred line B73 under ABA, JA, salt, drought, heat, and wounding stress revealed their specific expression patterns. Conclusively, this study unveiled the evolutionary pathway of ZmAP2/ERFs and its essential role in stress and developmental processes. The generated information will be useful for stress resilience maize breeding programs. Full article

APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1, APE1 or APEX1; redox factor-1, Ref-1) is a dual-functional enzyme with crucial roles in DNA repair, reduction/oxidation (redox) signaling, and RNA processing and metabolism. The redox function of Ref-1 regulates several transcription factors, such as NF-κB, STAT3, HIF-1α, and others, which have been implicated in multiple human diseases, including ocular angiogenesis, inflammation, and multiple cancers. To better understand how APE1 influences these disease processes, we investigated the effects of APEX1 knockdown (KD) on gene expression in human retinal endothelial cells. This abolishes both DNA repair and redox signaling functions, as well as RNA interactions. Using RNA-seq analysis, we identified the crucial signaling pathways affected following APEX1 KD, with subsequent validation by qRT-PCR. Gene expression data revealed that multiple genes involved in DNA base excision repair, other DNA repair pathways, purine or pyrimidine metabolism signaling, and histidine/one carbon metabolism pathways were downregulated by APEX1 KD. This is in contrast with the alteration of pathways by APEX1 KD in human cancer lines, such as pancreatic ductal adenocarcinoma, lung, HeLa, and malignant peripheral nerve sheath tumors. These results highlight the unique role of APE1/Ref-1 and the clinical therapeutic potential of targeting APE1 and pathways regulated by APE1 in the eye. These findings provide novel avenues for ocular neovascularization treatment. Full article

Therapies with the mechanistic target of rapamycin complex 1 (mTORC1) inhibitors are not fully curative for tuberous sclerosis complex (TSC) patients. Here, we propose that some mTORC1-independent disease facets of TSC involve signaling through redox factor-1 (Ref-1). Ref-1 possesses a redox signaling activity that stimulates the transcriptional activity of STAT3, NF-kB, and HIF-1α, which are involved in inflammation, proliferation, angiogenesis, and hypoxia, respectively. Here, we demonstrate that redox signaling through Ref-1 contributes to metabolic transformation and tumor growth in TSC cell model systems. In TSC2-deficient cells, the clinically viable Ref-1 inhibitor APX3330 was effective at blocking the hyperactivity of STAT3, NF-kB, and HIF-1α. While Ref-1 inhibitors do not inhibit mTORC1, they potently block cell invasion and vasculature mimicry. Of interest, we show that cell invasion and vasculature mimicry linked to Ref-1 redox signaling are not blocked by mTORC1 inhibitors. Metabolic profiling revealed that Ref-1 inhibitors alter metabolites associated with the glutathione antioxidant pathway as well as metabolites that are heavily dysregulated in TSC2-deficient cells involved in redox homeostasis. Therefore, this work presents Ref-1 and associated redox-regulated transcription factors such as STAT3, NF-kB, and HIF-1α as potential therapeutic targets to treat TSC, where targeting these components would likely have additional benefits compared to using mTORC1 inhibitors alone. Full article