Search Results (228)

The demand for ready-to-eat salads made from leafy vegetables such as wild rocket (Diplotaxis tenuifolia L.) continues to increase, driven by consumer preference for convenience foods with high levels of bioactive compounds. However, reducing the environmental impact of wild rocket production requires both organically enriched growing substrates and sustainable alternatives to conventional plastic packaging. This study assessed the effects of three cultivation substrates and three biodegradable packaging materials (polylactic acid (PL), cellulose kraft (CK), and kraft-reinforced polylactic acid (PLK)) on the postharvest performance of wild rocket stored at 4 °C for 7 and 14 days. Plants were grown in coco peat (CP), coco peat supplemented with livestock compost (90:10; CP+LC), and coco peat mixed with mushroom compost (50:50; CP+MC). Yield and key pre- and postharvest quality attributes, including nitrate accumulation, phenolic content, antioxidant capacity, colour, and weight loss, were evaluated. The CP+LC substrate resulted in the highest harvest yield, whereas CP promoted higher phenolic content and antioxidant capacity. Among the packaging materials, PLK provided the most balanced internal atmosphere, effectively reducing dehydration and condensation while preserving superior sensory quality after 14 days of storage. Overall, the combination of organic compost amendments, particularly CP+LC, with PLK bio-based packaging represents a promising and sustainable strategy for maintaining postharvest quality and reduce the environmental footprint of minimally processed wild rocket within short food supply chains. Full article

The Sichuan taimen (Hucho bleekeri) is a flagship species for the Yangtze River and is classified as critically endangered by the IUCN. Successful artificial breeding and conservation efforts are therefore essential for maintaining population stability. The early embryonic stage is the foundation of the entire life cycle and is critical for subsequent survival and growth. Here, we aimed to investigate gene-expression profiles across eight developmental stages through RNA-seq sequencing: fertilized egg, embryonic shield elevation, cleavage, blastula, gastrula, neurula, brain differentiation, and hatching. Time-series analysis revealed remarkable gene-expression changes between the cleavage and embryonic shield elevation, gastrula and blastula, and brain differentiation and hatching stages. The expression levels of cell cycle-related genes—including ccn2d, ccna2, cdk11, cdk17, cdka2, cdkl3, plk1, and others—decreased during embryonic development. Genes associated with muscle development, such as myl9, mylk, and tnnc2, were present in all stages and significantly enriched at hatching, while others were nearly absent during early development. In metabolic pathways, genes related to lipid metabolism and glycolysis were significantly expressed in the hatching stage. Regarding immune-related genes, complement genes were notably enriched at hatching, whereas cfh and cfb were expressed throughout development. Genes involved in adaptive immunity, such as mhc I, mhc II, tcr, and T-cell marker genes, were either not expressed or only weakly expressed in all stages. The results can provide insights into regulatory mechanisms underlying early embryonic development in fishes and provide general knowledge about salmonid development. Full article

Acrolein, a highly reactive environmental toxicant widely present in urban air and tobacco smoke, has been implicated in the development of multiple malignancies. In oral tissues, chronic acrolein exposure induces oxidative stress, inflammation, and genetic mutations, all of which are closely linked to the development of oral squamous cell carcinoma (OSCC). Although accumulating evidence indicates a strong association between acrolein exposure and OSCC, its prognostic significance remains poorly understood. In this study, we analyzed transcriptome data to identify differentially expressed genes (DEGs) between tumor and adjacent normal tissues, and screened acrolein-related candidates by intersecting DEGs with previously identified acrolein-associated gene sets. Functional alterations of these genes were assessed using Gene Set Variation Analysis (GSVA), and a protein–protein interaction (PPI) network was constructed to identify key regulatory genes. A prognostic model was developed using Support Vector Machine–Recursive Feature Elimination (SVM-RFE) combined with LASSO-Cox regression and validated in an independent external cohort. Among the acrolein-related DEGs, four key genes (PLK1, AURKA, CTLA4, and PPARG) were ultimately selected for model construction. Kaplan–Meier analysis showed significantly worse overall survival in the high-risk group (p < 0.0001). Receiver operating characteristic (ROC) curve analysis further confirmed the strong predictive performance of the model, with area under the curve (AUC) values of 0.72 at 1 year, 0.72 at 3 years, and 0.75 at 5 years. Furthermore, the high risk score was significantly correlated with a ‘cold’ immune microenviroment, suggesting that acrolein-related genes may modulate the tumor immune microenvironment. Collectively, these findings highlight the role of acrolein in OSCC progression, suggesting the importance of reducing acrolein exposure for cancer prevention and public health, and call for increased attention to the relationship between environmental toxicants and disease initiation, providing a scientific basis for public health interventions and cancer prevention strategies. Full article

Objectives: Although Aurora kinase A (AURKA) expression has been investigated in many cancer types, studies focusing on its role in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are limited. In this study, we examined the activity of AURKA and its substrates (PLK1, P53, and BRCA1) in HBV-HCC and cryptogenic hepatocellular carcinoma (Cr-HCC) cases. Methods: The study groups consisted of HBV-HCC, Cr-HCC, and healthy liver tissue cases. AURKA copy number variation (CNV) was analyzed using molecular methods. AURKA expression was evaluated by molecular and immunohistochemical (IHC) methods. AURKA substrates P53^Ser315, PLK1^Thr210, and BRCA1 were also analyzed by IHC. Results: There was no increase in AURKA gene copy number among the groups (2^−∆∆Ct < 2). AURKA level was significantly increased in both test groups (p < 0.001). At the protein level, AURKA was significantly higher in both cancer groups compared to the control group (p < 0.001). Phospho-P53^Ser315 levels were significantly higher in both HBV-HCC and Cr-HCC groups compared to the control group (p = 0.002 and p < 0.001, respectively). Cr-HCC cases also showed significantly higher levels compared to HBV-HCC (p = 0.025). For phospho-PLK1^Thr210, Cr-HCC cases showed statistically higher expression compared to both the control group and HBV-HCC cases (p = 0.001). Full article

Triple-Negative Breast Cancer (TNBC) remains the most aggressive breast cancer subtype, characterized by profound heterogeneity and a lack of effective targeted therapies. Although cytotoxic chemotherapy is the standard of care, the rapid emergence of resistance driven by cancer stem cells (CSCs), metabolic plasticity, and the tumor microenvironment limits long-term survival. This review highlights the paradigm shift in TNBC treatment from 2021 to 2025, moving beyond broad cytotoxicity to precision medicine. We first examine the limitations of earlier targeted therapies, such as PI3K/AKT/mTOR inhibitors, which failed due to compensatory feedback loops and toxicity. We then discuss emerging synthetic lethality strategies targeting the G2/M checkpoint (WEE1, ATR) and mitotic kinases (PLK1, TTK) to exploit genomic instability in TP53-mutant tumors. Furthermore, we explore how novel modalities like PROTACs and Antibody–Drug Conjugates (ADCs) are unlocking the “undrugged kinome,” including targets like TNIK, PTK7, and PAK4, which were previously inaccessible. Finally, we propose that future success lies in combinatorial strategies integrating these next-generation kinase inhibitors with ADCs and immunotherapies to dismantle therapeutic resistance. Full article

Objective: Identifying biomarkers that predict metastatic potential or guide treatment selection is critical for improving breast cancer (BC) management. Previously, we established the Mitotic Network Activity Index (MNAI) as a prognostic marker in BC. Here, we bioinformatically and experimentally evaluated MNAI as a biomarker for metastasis risk and therapeutic response. Methods: We used Kaplan–Meier and Cox proportional hazard regression analyses to assess the association between MNAI and distant metastasis-free survival (DMFS) across 14 published BC datasets. A total of 16 publicly available clinical trial datasets, including the I-SPY trials, were used to evaluate the predictive value of MNAI for treatment response. Additionally, wound-healing and transmembrane assays were conducted to determine the effects of PLK1, CHEK1, and BUB1 inhibition on BC cell migration and invasion. Results: High MNAI levels were strongly associated with shorter DMFS. Multivariate analysis further confirmed MNAI as an independent risk factor for DMFS, beyond estrogen receptor status and PAM50-based molecular subtypes. Functionally, pharmacologic disruption of the mitotic network using PLK1, CHEK1, or BUB1 inhibitors significantly reduced cell migration and invasion in MDA-MB-231 and BT-549 BC cell lines. Moreover, BC cells with high MNAI increased sensitivity to microtubule-targeting agents such as docetaxel, paclitaxel, and ixabepilone but increased resistance to tamoxifen, AKT1/2 inhibitors, and mTOR inhibitors. Consistent with these findings, analysis of 16 clinical trial cohorts revealed that patients with high MNAI achieved higher pathological complete response rates to taxane-containing and ixabepilone-based therapies. Conclusions: Our findings demonstrate the MNAI as a clinically actionable biomarker that can refine risk stratification and guide the selection of targeted or chemotherapy regimens, advancing precision medicine in BC management. Full article

Acute myeloid leukemia (AML) is one of the most aggressive types of leukemia, represented by the clonal proliferation of hematopoietic precursors, which mainly promotes quantitative and differentiation alterations, as well as normal hematopoiesis suppression. Throughout leukemogenesis, modifications may occur in several elements that make up cellular signaling pathways; among these, AURKA, AURKB, and PLK1 are key related regulators of mitotic progression and cellular proliferation. This study investigated the hematological profile and the expression of the AURKA, AURKB, and PLK1 genes in a cohort of individuals with AML, in order to understand their roles in the pathophysiology of the disease. The analyses revealed a significant hypoexpression of AURKA in the bone marrow of AML individuals compared to the control group (p = 0.0254) and AURKB showed no significant difference in bone marrow and peripheral blood samples. It was also observed a hyperexpression of PLK1 in bone marrow (p < 0.0001) and in peripheral blood (p = 0.0144). Our results also point to PLK1 as a potential biomarker for AML, since its hyperexpression did not differ with respect to gender, risk stratification, or age of the individuals. Finally, survival analyses indicate that AURKA expression in the bone marrow is associated with a protective factor and increased survival, and that those with higher expression of the three target genes had a lower mortality rate (p = 0.043). Full article

Colorectal cancer (CRC) therapy frequently relies on chemotherapeutic agents with high cytotoxicity, low selectivity, and suboptimal efficacy. Thus, the search for alternative therapeutic strategies for CRC continues. In the present work, the antitumor potential of a hybrid compound, which contains fragments derived from resveratrol and curcumin, was evaluated. These natural compounds are known by their antioxidant, chemopreventive, and chemotherapeutic properties. Different methodologic approaches were used to investigate cytotoxic, genotoxic, antiproliferative, and antioxidant effects of a hybrid compound, named PQM-162, on HCT-8 colorectal cancer cells. The results showed that PQM-162 displays radical scavenging capacity as demonstrated by DPPH assay. Furthermore, this substance reduced cell viability and inhibited cell cycle progression at G2/M in HCT-8 cells. Antiproliferative activity of PQM-162 was associated with its ability to modulate the expression of critical regulators of G2/M transition and mitosis progression such as PLK1, AURKB, and CDKN1A. Taken together, our data indicate that PQM-162 is a promising antitumor agent due to its disruption of the redox balance in cancer cells and its modulation of the expression of regulators of the cell cycle and mitotic apparatus. Full article

Polo-like kinase 1 (PLK1) is a serine/threonine kinase that orchestrates multiple critical events during mitosis, including centrosome maturation, spindle assembly, kinetochore–microtubule attachment, and cytokinesis. Dysregulation and overexpression of PLK1 are frequently observed in various cancers, correlating with increased proliferation, metastatic potential, and poor prognosis, which highlights its potential as a therapeutic target. Traditional small-molecule inhibitors have predominantly focused on the ATP-binding site of the N-terminal kinase domain, effectively inducing mitotic arrest and apoptosis in tumor cells; however, these compounds often suffer from limited selectivity and off-target toxicity. The C-terminal Polo-box domain (PBD), responsible for substrate recognition and subcellular localization, has emerged as an alternative and highly selective target for inhibitor design, enabling the disruption of protein–protein interactions critical for PLK1 function. Here, we present a comprehensive review demonstrating the potential inhibition of several compounds against PLK1. This work establishes a foundation for future preclinical development of small molecule-based therapeutics against PLK1-dependent malignancies. Full article

In this work, we report an efficient synthetic strategy for accessing novel 1,4-disubstituted-1,2,3-triazole-1,3-oxazole hybrids. The synthesis involves a two-step, three-sequence approach: a multicomponent reaction, subsequent oxidation, and the Van Leusen reaction. This operationally simple protocol proceeds under mild reaction conditions and allows the rapid assembly of structurally diverse heterocyclic systems. Three new hybrid molecules were synthesized and structurally characterized. To investigate their biological potential, we performed bioactivity prediction studies using cheminformatics tools. Polo-like kinase 3 (PLK3), a serine/threonine-protein kinase involved in cell cycle regulation and apoptosis, was identified as a potential molecular target, for which docking studies were performed, obtaining good ligand efficiency. Full article

Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase expressed in smooth muscle cells (SMCs), with emerging roles in regulating contraction. We hypothesize that PLK1 contributes to smooth muscle contractility in pudendal arteries (PA), small mesenteric arteries (SMA), and the corpus cavernosum (CC). Using male C57BL/6J mice, we assessed mRNA and protein expression of PLK1 in these tissues. In addition, the arteries and CC were mounted in myographs for isometric force measurement. We then investigated whether PLK1 regulates SMC contractility induced by phenylephrine (PE), U46619, and angiotensin II (Ang II) in arteries, and by PE, serotonin (5-HT), and electrical field stimulation (EFS; 1–16 Hz) in the CC, both in the presence and absence of the PLK1 inhibitor volasertib. PLK1 expression was confirmed in the SMA, PA, and CC by RT-qPCR or Western blotting. Notably, PLK1 inhibition significantly reduced Ang II-induced contraction in the PA and SMA and attenuated EFS-induced contraction at 2 and 4 Hz in the CC. In contrast, responses to PE, U46619, and 5-HT were unaffected by PLK1 inhibition. These results suggest that PLK1 selectively mediates contraction in response to Ang II and neurogenic stimuli. PLK1 may therefore represent a novel, stimulus-specific regulator of vascular and erectile smooth muscle contractility. Full article

Lung adenocarcinoma (LUAD) remains the most common subtype of non-small-cell lung cancer and a major cause of cancer mortality, with many patients lacking actionable mutations or durable responses to targeted or immune therapies. Here, we report an integrative analysis of TCGA LUAD transcriptomes (n = 598) seeded from a curated ferroptosis gene catalogue, yielding a compact six-gene signature (AQP4, CDCA3, HJURP, KIF20A, PLK1, UHRF1) with diagnostic, prognostic, and therapeutic relevance. The signature was consistently dysregulated in tumours versus normal lung and stratified patients into high- and low-risk groups with distinct survival outcomes (log-rank p < 0.0001), outperforming conventional staging when incorporated into multivariable models. Across ten machine learning algorithms, the panel achieved near-perfect tumour-normal classification (AUC 0.99–1.00), highlighting its translational potential for early detection. Functional analyses linked the signature to cell-cycle, angiogenic, and immune modulation, while exploratory drug-gene correlations identified PLK1 and other candidates as potential therapeutic targets. Together, these findings establish a biologically anchored six-gene panel that complements existing mutation-based classifiers and provides a framework for advancing diagnostic precision, prognostic refinement, and biomarker-guided therapeutic strategies in LUAD. Full article

Skin cancer remains a significant global health challenge, with rising incidence and associated mortality in late-stage and drug-resistant cases. This underscores a continuing need for more effective novel therapeutic options that can be utilized for efficient management of skin cancers. A promising approach involves exploiting novel targets, which are dysregulated in skin cancer, either alone or in combination with existing therapeutics. Among these, polo-like kinases (PLKs), a family of serine/threonine kinases, has emerged as promising candidates due to their essential role in cell cycle and maintaining genomic stability, key hallmarks of cancer. Within this family, polo-like kinase 4 (PLK4) stands out as a structurally distinct member and the master regulator of centriole duplication, ensuring this process occurs only once per cell division. Dysregulation of PLK4 can disrupt genomic integrity, contributing to tumorigenesis, thus making it a promising target for cancer management. Notably, PLK4 is frequently overexpressed in several cancers, including skin cancer, and its precise role in skin cancer is an area of current investigation. Further, several small-molecule PLK4 inhibitors such as centrinone, YLZ-F5, CFI-400945, and RP-1664 have demonstrated efficacy in targeting PLK4. Among these, CFI-400945 has advanced to clinical trials, where it has shown modest anti-cancer activity. In this review, we provide a comprehensive overview of the known functions of PLK4 in skin cancer. Additionally, we discuss potential mechanistic insights into PLK4′s involvement in skin cancer progression by extrapolating evidence from studies in other cancer types including colorectal cancer, thyroid cancer, lymphomas, leukemia, etc., while identifying gaps for future research. Full article

This review provides an overview of the most significant developments in gout pathophysiology research published in 2024. Thirteen studies were selected based on originality, scientific rigor, and potential clinical impact and grouped into four major categories: inflammation and pain mechanisms (LRRC8 anion channels, CXCL5-CXCR2 axis, CD38 and NAD⁺ metabolism, PLK1 and NLRP3 inflammasome localization, and IFN1 suppression), biomarkers and proteomics (scRNA-seq reveals monocyte and T-cell flare signatures, and Olink serum profiling reveals a proinflammatory signature in hyperuricemia and also identifies TNFSF14 as a novel flare biomarker, while a multi-omics integrative study implicates TRIM46 as a key causal gene), gut virome, and novel therapies (vagus nerve stimulation, biomimetic nanosystem, and restoration of Urate Oxidase (Uox) function). The studies selected focused primarily on work on subjects other than on hyperuricemia. The findings collectively expand our understanding of gout’s complex pathophysiology and highlight potential strategies for diagnosis, management, and innovative treatments. Full article

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article