Search Results (364)

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by aggressive tumor biology, extensive intratumoral heterogeneity, and profound resistance to standard therapies. While recurrent genetic alterations such as KRAS mutations are central to PDAC initiation, growing evidence demonstrates that epigenetic dysregulation is a critical determinant of disease progression, cellular plasticity, immune evasion, and therapeutic failure. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation, shape transcriptional programs without altering the underlying DNA sequence, rendering them dynamic and potentially reversible therapeutic targets. This review provides a comprehensive overview of key epigenetic proteins implicated in PDAC, encompassing writers, readers, and erasers of chromatin marks. Aberrant activity of histone methyltransferases and acetyltransferases, bromodomain-containing proteins, histone deacetylases, and demethylases orchestrates transcriptional reprogramming that promotes epithelial–mesenchymal transition, stem-like phenotypes, metabolic adaptation, and resistance to chemotherapy and radiotherapy. In parallel, epigenetic alterations within the tumor microenvironment contribute to stromal activation and immune suppression, further limiting therapeutic efficacy. We summarize recent advances in pharmacological targeting of epigenetic regulators and discuss the rationale for combination strategies integrating epigenetic inhibitors with cytotoxic agents, targeted therapies, and immunotherapies. Emphasis is placed on emerging experimental platforms—including patient-derived organoids, co-culture systems, and in vivo models—combined with multi-omic profiling and computational approaches to identify biomarkers of response and optimize therapeutic design. Collectively, this review highlights epigenetic regulation as a central and actionable vulnerability in PDAC and outlines future directions toward biomarker-guided, personalized epigenetic therapies aimed at overcoming resistance and improving clinical outcomes. Full article

The manuscript describes an optical sensing microplate for the high-throughput screening of imidazolinone herbicides in soil extracts. As far as we know, imprinted proteins (IPs) specific to imidazolinone herbicides have not been synthesized and used as a recognition element for their solid-phase extraction before. Imprinted bovine serum albumin (BSA) and glucose oxidase (GOx) were synthesized in the presence of imazamox as a template and then these IPs were immobilized at the bottom of microplate wells. The sorption capacity (Q) of aminated silica nanoparticles modified by IPs (IP–BIS) was 6.38 mg g⁻¹ while the imprinting factor ($IF$) equaled 2.6. The concentration of imazamox was determined by a “turn-off” solid-phase assay using alloyed CdZnSeS/ZnS quantum dots (QDs) as a component of fluorescent substrate. Alloyed CdZnSeS/ZnS QDs were stabilized in an aqueous phase by positively charged cysteamine that, as far we know, had not been used as this type of ligand before. Our method allows for determining the concentration of imazamox in the range of 0.5–9.2 μg mL⁻¹, with a limit of quantification limit of quantitation (LOQ) equal to 0.45 μg mL⁻¹ The sensing microplate enables parallel detection of up to 96 samples containing herbicides using standard fluorescence microplate readers or smartphones. The paper describes how such sensing microplates can be used for the analysis of artificially contaminated soil samples. The proposed approach combines pre-concentration of analyte at the IPs with its subsequent determination on a single analytical platform, thus allowing for both highly sensitive determination in laboratory conditions and mass screening in the field. Full article

Lateral flow assays (LFAs) are among the most successful technologies for point-of-care and at-home testing, but further advances are needed to reduce costs and accelerate development. Alpaca-derived nanobodies (Nbs), single-domain antibody fragments, are promising immunoassay reagents across diverse applications. Their small size and ease of recombinant production make them particularly well suited for diagnostics. Here, we present a paper-based LFA targeting the SARS-CoV-2 nucleocapsid (N) protein that exclusively uses Nbs for direct antigen detection. We also demonstrate in-house synthesis of Nb-coated gold nanoparticles, enabling instrument-free visual readout and detection of N protein down to 40 ng/mL. This design avoids components that require mammalian cell culture and can be produced entirely from in-house reagents, simplifying manufacturing and lowering component costs. Because the assay is read visually without an external reader, it is well suited for deployment in resource-limited settings. Together, these results highlight the speed and practicality of developing Nb-based LFAs and suggest a broadly applicable strategy for detecting other clinically important disease biomarkers. Full article

The half-life of proteins is determined by the “information” carried within specific regions of the protein. Lysine methylation is an emerging post-translational modification that can act at the decision node. In contrast to the charge-neutralizing effects of lysine acylation, methylation maintains the positive charge of the lysine residue, allowing for the presence of multiple methylation states (Kme1/2/3). This property enables the “reading” of the methylation state by “methyl lysine readers.” Although the methyl group is chemically stable, the methylation is enzymatically reversible by lysine demethylases. In this review, we conceptualize the “methyl lysine” as an “information”-containing “signal” at the decision node. The “information” is composed of the interplay between the “competition” among the same site modifications, the “methylation-dependent degron” or “methyl degrons,” the “steric blockade” or “methyl shields,” and the “changes in spatial routing” or “methyl routing cues.” In this review, we discuss the emerging evidence within these three types of functional methyl lysine. Full article

Lactylation serves as a vital link between cellular metabolism and epigenetic regulation and plays a pivotal role in muscle biology. Muscle tissue is the primary site of lactate production; its unique metabolic environment confers dynamism, specificity and functional diversity for lactylation. Under physiological conditions, lactylation regulates myocyte energy metabolism, proliferation, differentiation, and exercise adaptation through a dynamic “writer–eraser–reader” mechanism. In pathological states, lactate imbalance directly contributes to the progression of various muscular disorders. For instance, diminished histone lactylation during muscle aging suppresses the expression of genes critical for DNA repair and protein homeostasis. Aberrant lactylation is involved in the development of insulin resistance and diabetic cardiomyopathy. Furthermore, lactylation exerts dual effects in cardiovascular diseases; it provides protection by enhancing the transcription of repair genes and simultaneously aggravates injury by promoting processes such as fibrosis and ferroptosis. Collectively, these findings underscore the importance of lactylation in muscular pathologies and provide a theoretical foundation for the development of therapies that target this modification process. As the regulatory mechanisms of lactylation have become clearer, precise interventions targeting specific modification sites are expected to open new therapeutic avenues for muscular diseases. Full article

Background/Objectives: The RNA-binding protein CELF1 is crucial for cardiac development, but its role in cardiomyocyte hypertrophy is unclear. This study investigates the effects of acute CELF1 knockdown on alternative splicing and hypertrophic growth in cardiomyocytes. Methods: Neonatal rat cardiomyocytes (NRCMs) were transfected with two siRNAs targeting CELF1. Hypertrophy was assessed by cell size and expression of hypertrophic markers via qPCR and Western blot. RNA sequencing was performed in NRCMs to identify alternative splicing events. Tead1 function was tested by knockdown in NRCMs. Selected mechanistic assays were performed primarily in HeLa cells. Results: CELF1 knockdown in NRCMs increased cardiomyocyte size and upregulated hypertrophic markers, while its overexpression restored the phenotype. RNA-seq revealed that CELF1 knockdown alters the alternative splicing pattern. Specifically, the splicing of the transcription factor Tead1 shifted from the full-length long Tead1 isoform (Tead1-L) to the exon 4-skipped short isoform (Tead1-S). In HeLa cells, CELF1 interacted with hnRNPC, an m⁶A reader and splicing factor, and CELF1 perturbation correlated with changes in global m⁶A abundance. Conclusions: These findings suggest that CELF1 regulates hypertrophic phenotypes in cardiomyocytes and is associated with alternative splicing of Tead1. Full article

Basidiomycete mushrooms contain complex β-D-glucans which act as immunomodulator, immune stimulants and anti-cancer agents, which can be either free or bound to proteins. The present report consists of a novel and intrinsic synchronous fluorescence and phosphorescence assay method for β-D-glucans. This analytical technique was carried out by a spectrofluorometer in the range of 250 to 750 nm with a Δλ range of 5–30 nm which exhibited peaks at 492, 540 and 550 nm by using β-D-glucan from Euglena gracilis as a standard. A micro and high-throughput method based on a microplate fluorescence reader was devised with a excitation and emissions λ of 420 nm and 528 nm, respectively. This assay method revealed some advantages over the reported colorimetric methods, since it is a non-destructive assay method of β-D-glucans in samples with a linearity range of 0–14 μg/well, correlation coefficient (r2) of 0.9961, LOD of 0.973 μg/well, LOQ of 2.919 μg/well, greater sensitivity, fast, a high-throughput method and very economical. β-D-glucans of several mushrooms (i.e., Poria coccus, Auricularia auricula, Ganoderma lucidium, Pleurotus ostreatus, Cordyceps sinensis, Agaricus blazei, Polyporus umbellatus, Inonotus obliquee) were purified by using a sequence of various solvent extractions, quantified by either spectrofluorometer or fluorescence microtiter plate reader assay and compared with Congo red assay method. Three-dimensional spectra measurements were carried out on β-D-glucans from commercial sources and medicinal mushroom strains. FTIR spectroscopy was selected to investigate the structural properties of β-D-glucans in these mushroom samples. Therefore, the present assay method is simple, fast, cheap and non-destructive for β-D-glucans from medicinal mushrooms as well as from commercial sources. Full article

Background/Objectives: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders. Despite its multifactorial etiology, PD pathophysiology shared specific features such as cytoplasmic α-synuclein inclusions, oxidative stress, mitochondrial dysfunction, and impaired autophagy. Bromodomain and Extra-Terminal domain (BET) proteins, functioning as epigenetic readers, have recently emerged as promising therapeutic targets due to their regulatory role in redox homeostasis, neuroinflammation, and autophagy. However, their potential involvement in PD pathophysiology remains largely unexplored. Therefore, we aimed at evaluating whether BET modulation could ameliorate the parkinsonian phenotype in two cellular models. Methods: Differentiated SH-SY5Y and N1E-115 neuronal cells were exposed to rotenone toxin to mimic PD phenotype and co-treated with the small BET inhibitor JQ1. Results: BET inhibition significantly counteracted rotenone-induced cell death, neuromorphological alterations, and α-synuclein accumulation. These protective effects were accompanied by restoration of redox balance, as indicated by enhanced activation of the antioxidant system and suppression of the pro-oxidant NADPH oxidase complex. Moreover, JQ1 treatment alleviated mitochondrial dysfunction and corrected autophagy impairments triggered by rotenone. Conclusions: These data highlight a novel role for BET proteins in neurodegeneration, suggesting that their modulation may represent a promising approach to counteract PD neuropathology. Full article

This review examines the application of Artificial Intelligence (AI) in the discovery and optimisation of neuroprotective natural products (NPs) for neurodegenerative diseases (NDDs), emphasising the transition from general computational drug discovery to AI-specific approaches designed to address the chemical complexity and bioactivity profiles of natural compounds. The discussion encompasses relevant datasets, AI models, illustrative case studies, and emerging protein and biological targets that may serve as potential points of intervention for the prevention and treatment of NDDs. The review is organised to guide the reader from foundational knowledge to applied strategies; it begins by outlining the chemical and biological principles underlying neuroprotective NPs, then presents AI-driven computational frameworks for NP discovery, followed by a detailed examination of recent case studies in NDDs. Subsequent sections address the key challenges, opportunities, and future directions in the field, concluding with an evaluation of prospects for interdisciplinary collaboration across medicinal chemistry, neuroscience, and artificial intelligence. Full article

N6-methyladenosine (m6A), a predominant and reversible modification of mammalian RNA, plays a critical role in regulating growth, development, and metabolism. While methyltransferase-like 14 (METTL14) is an essential component of the m6A methyltransferase complex, its specific function in regulating milk fat metabolism in dairy goats remains unexplored. This study therefore aimed to elucidate the role of METTL14 in lipid metabolism within dairy goat mammary epithelial cells (GMECs). METTL14 overexpression significantly promoted the synthesis of TAG (Triacylglycerol) and TC (Total cholesterol), as well as lipid droplet accumulation in GMECs. Furthermore, METTL14 upregulated CCAAT enhancer binding protein beta (CEBPB) expression at both the mRNA and protein levels by directly inducing m6A modification on its transcripts. Finally, we confirmed that m6A modification occurs specifically at site 1662 of CEBPB mRNA, and the “Readers” YTH N6-methyladenosine RNA binding protein F1 and F3 (YTHDF1/3) were found responsible for the m6A site recognition and interpretation. This study demonstrated that METTL14 facilitates lipid synthesis and deposition in GMECs. Mechanistically, METTL14 installs the m6A modification at site 1662 of CEBPB transcripts. This m6A mark is specifically recognized by the readers YTHDF1 and YTHDF3, which promote the translation of CEBPB mRNA, thereby upregulating its expression. Full article

N6-methyladenosine (m⁶A) constitutes the most prevalent nucleotide modification within eukaryotic messenger RNA (mRNA). Variations in m⁶A levels are associated with numerous human diseases and health conditions, including various forms of cancer, diabetes, neurological disorders, male infertility, and obesity. Nevertheless, the molecular mechanisms underpinning the recognition of m⁶A by different ‘reader’ proteins remain incompletely elucidated. In this study, we used phage display to identify key sequence features that methyl readers recognize in m⁶A. This study shows that m⁶A modifications affect the mRNA interactome. A peptide motif recognizing m⁶A in DRACH sequences suggests a common recognition mechanism, though proteins may use different methods to detect m⁶A in less accessible areas. The sequence of the hnRNP A1 RRM domain that aligns with the newly discovered m⁶A-binding peptide, m1p1, is crucial for the binding of m⁶A-modified RNAs, indicating a strong link between the m1p1 sequence and m⁶A recognition, which is key for recognizing m⁶A-modified, unstructured RNAs. Gaining a comprehensive understanding of the evolutionary influence of m⁶A on its reader proteins may facilitate the identification of additional m⁶A readers. These signature peptides could enhance theranostic approaches across cancers, enabling more targeted therapies. Full article

The conceptual understanding of genetic information has evolved from early philosophical speculation to the molecular precision of contemporary biology. Initial debates over the nature of heredity, including Mendel’s hereditary factors and the longstanding protein versus nucleic acid controversy, underscored the difficulty of identifying the true substrate of inheritance. Subsequent discoveries, including reverse transcription, protein-based infectivity (prions), transposable elements, and the regulatory functions of non-coding RNAs, revealed molecular processes that operate at the boundaries of, or alongside, Crick’s original formulation of the Central Dogma of Molecular Biology. Importantly, these findings do not violate the directional rules of information transfer defined by the Central Dogma (DNA → RNA → protein), but instead reshape how, when, and under what constraints these canonical flows are executed in living systems. Epigenetic and epigenetic-like mechanisms, including DNA methylation, histone modifications, chromatin topology, non-canonical DNA conformations, and cytoplasmic inheritance, introduce regulatory layers that modulate information flow without constituting independent information matrices. In parallel, genome innovation, through de novo gene birth, and genome erosion, through pseudogenization, demonstrate that the repertoire of DNA → RNA → protein pathways is itself evolutionarily dynamic. This narrative integrative review reconstructs the historical milestones that culminated in the Central Dogma and synthesizes subsequent discoveries that expand its functional realization. By revisiting the Central Dogma through an extended, holistic lens, this article argues that DNA, RNA, and proteins function not only as carriers of genetic information, but also as active participants in its regulation, contextualization, and evolutionary diversification, without departing from the core directional principles originally articulated by Crick. For reader convenience, a dedicated section entitled “Abbreviations and Key Molecular Terms” is provided at the end of the manuscript to facilitate navigation and interdisciplinary accessibility. Full article

Emerging evidence suggests that viral infections may contribute to the onset and progression of Alzheimer’s disease (AD) and other forms of dementia. Understanding the mechanism of viral involvement in the pathogenesis of AD and related dementia (ADRD) could contribute to reducing the burden caused by these conditions, which affect a large portion of the aging population. Some studies indicate the link between AD and viral infections, notably coronaviruses and herpesviruses. In AD, excessive production of reactive oxygen species (ROS) results in the modifications of lipids, proteins, and nucleic acids, contributing to synaptic dysfunction and cognitive impairments. Experimental evidence suggests that viral infections linked to ADRD induce the cellular production of ROS, possibly contributing to the pathogenesis of these conditions. Despite significant advances in defining the roles of ROS in neurological disorders and viral infections, the specific roles of ROS in virus-associated ADRD have not been thoroughly investigated. The main objective of this review article is to comprehensively provide information on the experimental evidence for the production of ROS by viruses to help the readers investigate the role of ROS in the relationship between viral infections with ADRD. Full article

YT521-B homology (YTH) domain-containing RNA-binding proteins, the earliest identified and most well-known m⁶A reader proteins, play important roles in post-transcriptional regulation of plant growth and development as well as stress response by specifically recognizing m⁶A-modified RNA and subsequently recruiting downstream effector proteins to mediate the biological effects of m⁶A modification in eukaryotes. In recent years, the identification and functional characterization of YTH family proteins in woody plants have significantly advanced. However, a systematic identification of the YTH proteins has not yet been reported in Salix suchowensis (S. suchowensis), an early-flowering shrub serving as a valuable model for basic genetic research in woody plants. In this study, we identified 11 YTH genes, named SsYTH1-SsYTH11, located on 9 of 19 chromosomes in S. suchowensis. All proteins with a highly conserved YTH domain were classified into 4 distinct subfamilies based on the phylogenetic analysis. The MEME analysis showed that two conserved motifs, motif 1 and motif 2, were distributed in most SsYTH proteins. Promoter cis-acting element analysis of these proteins suggested a potential close association with abiotic stress and hormones. Subsequently, expression analysis following abscisic acid (ABA) and jasmonic acid (JA) treatments demonstrated significant differential expression of several SsYTH genes, thereby establishing a basis for further exploration of the YTH function in S. suchowensis and contributing to the broader understanding of epigenetic regulation in woody plants. Full article

Epstein–Barr virus (EBV) infection is closely associated with gastric cancer, yet its role in m6A-dependent gene regulation remains poorly understood. In this study, we investigated how EBV infection alters the m6A methylation pattern in gastric cancer cells and examined its impact on TSC22D1 mRNA stability through interaction with the m6A reader protein YTHDF1. m6A RNA immunoprecipitation sequencing (MeRIP-seq) revealed a significant reduction in m6A methylation of TSC22D1 in EBV-infected gastric cancer cells (AGS-EBV) compared with EBV-negative cells (AGS). Moreover, YTHDF1 knockdown increased both the stability and expression of TSC22D1. These findings demonstrate that YTHDF1 binds to TSC22D1 mRNA and promotes its m6A-dependent degradation. Collectively, our results suggest that EBV infection modulates m6A modification to regulate gene stability and identify the YTHDF1–TSC22D1 axis as a potential therapeutic target in EBV-associated gastric cancer. Full article