Search Results (1,951)

Post-translational modifications (phosphorylation and glutathionylation) not only assure protein diversity but are also responsible for the controlling of the biological activity of selected proteins in health and disease. The aim of the study was to monitor the profile of changes in molecular weight of proteins undergoing selected post-translational modifications by measurement of the intensity of phosphorylation and glutathionylation within the pregnancy course and parturition in cows with and without the retention of foetal membranes. The intensity of selected post-translational modifications was measured in bovine placental tissues collected during pregnancy (2nd, 4th, 5th, and 7th month, n = 4 per month) and parturition (not-retained foetal membranes (NRFM, n = 6) and retained foetal membranes (RFM, n = 6). Placental tissues were homogenised and used for the Phosphoprotein Phosphate Estimation Assay Kit and Western blotting analyses with adequate antibodies. The content of phosphorylated proteins was significantly higher (p < 0.05) in the 2nd month as compared to other months, both in the maternal and foetal parts of the placenta. Moreover, no significant differences were observed between NRFM and RFM samples. The results of Western blotting showed the shift in molecular weight and indirect content of phosphorylated selected amino acids. Further research on the role of post-translational modifications in pregnancy and parturition may give new insight into their biochemical regulation. Full article

Huntingtin (HTT) is a large, ubiquitously expressed scaffold protein that participates in multiple cellular processes, including vesicular transport, transcriptional regulation, and energy metabolism. The mutant form of HTT (mHTT), characterized by an abnormal polyglutamine (polyQ) expansion in its N-terminal region, is the causative agent of Huntington’s disease (HD), a progressive neurodegenerative disorder. Current therapeutic efforts for HD have primarily focused on lowering HTT levels through gene silencing or promoting mHTT degradation. However, accumulating evidence suggests that post-translational modifications (PTMs) of HTT—such as phosphorylation, ubiquitination, acetylation, and SUMOylation—play pivotal roles in modulating HTT’s conformation, aggregation propensity, subcellular localization, and degradation pathways. These modifications regulate the balance between HTT’s physiological functions and pathological toxicity. Importantly, dysregulation of PTMs has been linked to mHTT accumulation and selective neuronal vulnerability, highlighting their relevance as potential therapeutic targets. A deeper understanding of how individual PTMs and their crosstalk regulate HTT homeostasis may not only provide mechanistic insights into HD pathogenesis but also uncover novel, more specific strategies for intervention. In this review, we summarize recent understanding on HTT PTMs, discuss their implications for disease modification, and outline critical knowledge gaps that remain to be addressed. Full article

Cancer remains one of the most pressing health challenges of the 21st century, with rising global incidence underscoring the need for innovative therapeutic strategies. Despite significant advances in biotechnology, curative outcomes remain limited, prompting interest in integrative approaches. Ayurveda, the traditional Indian system of medicine, suggests a holistic therapeutic framework that is now gaining molecular validation in oncology. In this review, the literature was systematically collected and analyzed from major databases, including PubMed, Scopus, and Web of Science, encompassing studies across ethnopharmacology, biochemistry, and cancer biology. The analysis focused on Ayurvedic phytochemicals that modulate ADP-ribosylation (ADPr), a dynamic post-translational modification central to DNA repair, chromatin organization, and cellular stress responses, with particular emphasis on poly (ADP-ribose) polymerase (PARP)-mediated pathways and their oncological relevance. We have also explored the role of p53, a key stress-response regulator intricately linked to ADPr dynamics, which acts as a downstream effector integrating these molecular events with cell fate decisions. Evidence indicates that several Ayurvedic compounds, including curcumin, resveratrol, and withaferin A, influence PARP–p53 signaling networks, thereby modulating DNA repair fidelity, apoptosis, and tumor adaptation. The review further addresses challenges related to the poor solubility of these phytochemicals and highlights recent advances in Phyto-nanomedicine-based delivery systems that enhance their stability and therapeutic efficacy. Overall, the synthesis of Ayurvedic pharmacology with molecular oncology reveals mechanistic insights that may inform the rational development of novel, mechanism-driven cancer therapeutics. Full article

Omics approaches have advanced insight into molecular mechanisms of human obesity. We reviewed transcriptomic studies published between January 2020 and June 2025 that used human tissues or human cell lines and applied high-throughput RNA methods. Across these works three convergent themes emerged: (1) immune–inflammatory activation—particularly interferon-stimulated and innate immune signatures—linked to insulin resistance and visceral adiposity; (2) dysregulation of lipid and energy-metabolism pathways, including reduced lipolysis and β-oxidation in adipose tissue and liver; and (3) epigenetic and post-transcriptional regulation mediated by DNA methylation, histone modification, long noncoding RNAs, microRNAs and circular RNAs. Multi-omics integration (transcriptome with proteome, metabolome and microbiome) improved mechanistic interpretation and biomarker discovery but was limited by cohort heterogeneity and technical variation. We conclude that standardized, integrative multi-omics analyses in well-characterized, longitudinal human cohorts are required to translate molecular signatures into robust biomarkers and personalized therapeutic strategies for obesity. Full article

Cholesterol is an essential lipid in the human body, involved in critical physiological processes such as cell membrane composition and hormone synthesis. The homeostasis of cholesterol is vital for the normal functioning of the organism. Reverse Cholesterol Transport (RCT) is a core mechanism maintaining this balance, and ABCA1, as a key membrane transporter, plays a decisive role in RCT by mediating cholesterol efflux to HDL precursors, thereby promoting the initial formation of HDL. The regulatory mechanism of ABCA1 is extremely complex, with its regulation mainly occurring through two dimensions: transcriptional expression and post-translational modification. Currently, clinical drugs for regulating cholesterol are dominated by statins, supplemented by ezetimibe, PCSK9 inhibitors, and others. However, these drugs have certain limitations, and research on ABCA1-targeted drugs is relatively scarce. Therefore, summarizing the research progress on the regulatory mechanism of ABCA1 is expected to provide important insights for the development of new therapies to maintain cholesterol homeostasis. Full article

Alzheimer’s disease is driven by multiple molecular drivers, including the pathological behavior of two intrinsically disordered proteins, amyloid-β (Aβ) and tau, whose aggregation is regulated by sequence-encoded ensembles and liquid–liquid phase separation (LLPS). This review integrates recent advances in biophysics, structural biology, and computational modeling to provide a multiscale perspective on how sequence determinants, post-translational modifications, and protein dynamics regulate the conformational landscapes of Aβ and tau. We discuss sequence-to-ensemble principles, from charge patterning and aromatic binders to familial mutations that reprogram structural ensembles and modulate LLPS. Structural studies, including NMR, SAXS, cryo-EM, and cryo-electron tomography, trace transitions from disordered monomers to fibrils and tissue-level structures. We highlight experimental challenges in LLPS assays, emerging standards for reproducibility, e.g., LLPSDB, PhaSePro, and FUS benchmarks, and computational strategies to refine and condensate modeling. Finally, we explore the therapeutic implications, including condensate-aware medicinal chemistry, ensemble-driven docking, and novel insights from clinical trials of anti-Aβ antibodies. Together, these perspectives underscore a paradigm shift toward environment- and ensemble-aware therapeutic design for Alzheimer’s and related protein condensation disorders. Full article

The human Ccr4–Not complex is a central regulator of post-transcriptional gene regulation, impacting on translation and mRNA degradation. In mRNA degradation, Ccr4–Not participates in the shortening of the mRNA poly(A)-tail via two catalytic subunits. The Caf1 nuclease is encoded by the highly similar paralogues CNOT7 or CNOT8. In addition to its poly(A)-specific ribonuclease activity, this subunit also provides a structural role by binding Ccr4, the second catalytic nuclease subunit encoded by the paralogues CNOT6 or CNOT6L. To facilitate investigations into the roles of the Caf1 subunit, and to complement genetic tools, we set out to identify inhibitors of the enzymatic activity of Caf1/CNOT7. To this end, we screened a library of 10,880 chemically diverse, drug-like compounds using a fluorescence-based biochemical assay. This effort led to the discovery of 15 inhibitors of Caf1/CNOT7 with biochemical IC₅₀ values below 25 μM. Molecular docking was performed to explore potential binding modes of these compounds. The compounds reported here may be useful to differentiate between catalytic and non-catalytic roles of Caf1/CNOT7. In addition, they may be valuable starting points for the development of more potent inhibitors of the Caf1/CNOT7 poly(A)-selective ribonuclease. Full article

Cardiometabolic diseases, including cardiovascular disorders and type 2 diabetes mellitus, are the leading cause of morbidity and mortality worldwide, placing a significant burden on healthcare systems. Although advances in imaging and risk stratification have improved disease management, conventional diagnostic and prognostic tools often lack the requisite sensitivity and specificity for early and precise risk stratification. This limitation stems from their poor ability to capture the full molecular complexity of these conditions, underscoring an urgent need for innovative biomarkers to bridge these gaps. MicroRNAs, small non-coding RNAs that regulate gene expression post-transcriptionally, have emerged as promising candidates. Their characteristics offer several advantages over traditional methods, including exceptional stability in biological fluids, strong tissue and disease specificity, and the ability to reflect dynamic pathological changes. These unique features enable miRNAs to detect subtle molecular alterations that may precede clinical symptoms, thereby overcoming key limitations of current diagnostic approaches. Altered circulating miRNA profiles have been linked to pathological processes such as endothelial dysfunction, inflammation, oxidative stress, and maladaptive cardiac remodeling. This review provides a comprehensive overview of the current evidence supporting the diagnostic and prognostic role of circulating miRNAs in cardiometabolic disease. We highlight their potential as early detection biomarkers, tools for patient stratification, and indicators of therapeutic response. Furthermore, we discuss key limitations to clinical translation, including methodological variability, challenges in sample handling, differences in normalization strategies, and platform-dependent quantification inconsistencies. Overcoming these obstacles and achieving robust large-scale clinical validation will be essential to fully harness the potential of miRNAs as next-generation molecular signatures in precision medicine. Full article

N-glycosylation, a crucial eukaryotic post-translational modification, has been extensively studied for its significance in the physiology and virulence processes of plant pathogens over the last decade. This review systematically analyzes the functions of N-glycosylation-related endoplasmic reticulum (ER) proteins in regulating plant pathogen processes, including mycelial growth, conidial development, host penetration as well as colonization, pathogenicity, cell wall integrity and host immune evasion. By modifying the structure and function of target proteins, these ER-localized proteins regulate essential developmental events in pathogens while concurrently mediating interactions between pathogens and plants, influencing pathogens’ growth and disease-causing potential. Future research requires the systematic delineation of glycosylation-regulated protein networks by multi-omics integration technologies and the elucidation of their functional processes using molecular genetics methodologies, thereby establishing a robust theoretical foundation for the development of novel biological fungicides. Full article

Adenomyosis (AM) is a hormonally responsive uterine disorder defined by ectopic endometrial tissue within the myometrium, causing pain, abnormal bleeding, and subfertility. Non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—are post-transcriptional regulators implicated also in uterine remodeling. We systematically reviewed original studies evaluating ncRNAs in AM using human samples, in vitro and animal models, or bioinformatic approaches. Data sources included PubMed and Google Scholar (inception up to 10 August 2025). Forty-one studies were included and synthesized across mechanistic, diagnostic, and translational domains. miRNAs (n = 31) were the most studied subclass, followed by lncRNAs (n = 10) and circRNAs (n = 5). Recurrent miRNAs such as miR-10b and miR-30c-5p (downregulated, inhibitory) and miR-145 (upregulated, promotive) regulate epithelial invasion, epithelial–mesenchymal transition, and cytoskeletal remodeling via PI3K–AKT/MAPK and Talin1 signaling. The let-7a/LIN28B axis governed estrogen-sensitive proliferation in the junctional zone, while miR-21 exhibited compartment-specific roles in decidualization and ectopic cell survival. Extracellular-vesicle (EV)-bornemiRNAs (e.g., miR-92a-3p, miR-25-3p, miR-4669) contributed to immune polarization and show early diagnostic potential. lncRNAs and circRNAs acted via chromatin modifiers and ceRNA networks. Most findings remain at the discovery stage. Convergent dysregulation was observed in key signaling pathways, including JAK–STAT, Wnt/β-catenin, and Hippo–YAP. ncRNAs regulate critical axes of invasion, proliferation, immune modulation, and hormonal response in AM. Targets with preliminary causal support—miR-10b/ZEB1, let-7a/LIN28B, and miR-145/Talin1—warrant further validation. Circulating miRNAs—especially in EVs—offer promise for non-invasive diagnosis. Full article

The kidney’s intricate physiology relies on finely tuned gene regulatory networks that coordinate cellular responses to metabolic, inflammatory, and fibrotic stress. Beyond protein-coding transcripts, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators of renal biology. By modulating transcriptional, post-transcriptional, and epigenetic pathways, ncRNAs govern podocyte integrity, tubular adaptation, intercellular signaling, and immune activation. Dysregulation of these networks is now recognized as a hallmark of major kidney diseases, ranging from diabetic nephropathy and acute kidney injury to chronic kidney disease, glomerulopathies, and polycystic kidney disease. Mechanistic studies have revealed how pathogenic ncRNAs drive apoptosis, inflammation, fibrosis, and cystic remodeling, while protective ncRNAs mitigate these processes, highlighting their dual roles as both disease mediators and therapeutic targets. The exceptional stability of ncRNAs in urine, plasma, and exosomes further positions them as minimally invasive biomarkers with diagnostic and prognostic value. Translational advances include anti-miR and mimic-based therapies (e.g., lademirsen targeting miR-21, miR-29 mimics, anti-miR-17 oligonucleotides), alongside lncRNA silencing strategies, although challenges in delivery, safety, and redundancy remain significant. This review integrates molecular mechanisms with translational perspectives, providing a comprehensive synthesis of how ncRNAs shape renal pathophysiology. By bridging mechanistic insights with emerging diagnostic and therapeutic applications, we highlight the potential of ncRNAs to transform nephrology, paving the way for biomarker-driven precision medicine and novel interventions aimed at intercepting kidney injury at its regulatory roots. In clinical terms, ncRNA-based biomarkers and therapeutics promise earlier detection, more precise risk stratification, and individualized treatment selection within precision nephrology. Full article

Eragrostis nindensis is a resurrection grass capable of surviving near-complete desiccation. We compared non-senescent leaf tissue (NST) and senescent leaf tissue (ST) to investigate the cellular and molecular basis of desiccation tolerance and senescence. NST recovered fully after drying, while ST failed to regain viability. Integrated transcriptomic (using RNA-Seq), lipidomic (using LC-MS), and ultrastructural (Transmission Electron Microscopical) analyses revealed that NST maintain RNA processing, protein folding, and translational activity during desiccation. Lipidomic data and ultrastructure showed preferential accumulation of polyunsaturated triacylglycerols (TAGs) and lipid droplets in NST, supporting membrane protection and energy buffering. In contrast, ST showed cellular collapse, reduced oleosin protein accumulation, and signatures of senescence. These findings highlight the importance of post-transcriptional and post-translational regulation, as well as lipid metabolism, in preserving cellular integrity during desiccation in this species. Full article

Background/Objectives: Bacterial blight (BB) represents one of the most devastating diseases threatening global rice production. Exploring and characterizing disease resistance (R) genes provides an effective strategy for controlling BB and enhancing rice resilience. Common wild rice (Oryza rufipogon) serves as a valuable reservoir of genetic diversity and disease resistance resources. In this study, we identified and functionally characterized a novel NLR gene, YPR1, from common wild rice (Oryza rufipogon), which exhibited significant spatial, temporal, and tissue-specific expression patterns. Methods: Using a combination of conventional PCR, RT-PCR, bioinformatics, transgenic analysis, and CRISPR/Cas9 gene-editing approaches, the full-length YPR1 sequence was successfully cloned. Results: The gene spans 4689 bp with a coding sequence (CDS) of 2979 bp, encoding a 992-amino acid protein. Protein domain prediction revealed that YPR1 is a typical CNL-type NLR protein, comprising RX-CC_like, NB-ARC, and LRR domains. The predicted molecular weight of the protein is 112.43 kDa, and the theoretical isoelectric point (pI) is 8.36. The absence of both signal peptide and transmembrane domains suggests that YPR1 functions intracellularly. Furthermore, the presence of multiple phosphorylation sites across diverse residues implies a potential role for post-translational regulation in its signal transduction function. Sequence alignment showed that YPR1 shared 94.02% similarity with Os09g34160 and up to 96.47% identity with its closest homolog in the NCBI database, confirming that YPR1 is a previously unreported gene. To verify its role in disease resistance, an overexpression vector (Ubi–YPR1) was constructed and introduced into the BB-susceptible rice cultivar JG30 via Agrobacterium tumefaciens-mediated transformation. T₁ transgenic lines were subsequently inoculated with 15 highly virulent Xanthomonas oryzae pv. oryzae (Xoo) strains. The transgenic plants exhibited strong resistance to eight strains (YM1, YM187, C1, C5, C6, T7147, PB, and HZhj19), demonstrating a broad-spectrum resistance pattern. Conversely, CRISPR/Cas9-mediated knockout of YPR1 in common wild rice resulted in increased susceptibility to most Xoo strains. Although the resistance of knockout lines to strains C7 and YM187 was comparable to that of the wild type (YP^WT), the majority of knockout plants exhibited more severe symptoms and significantly lower YPR1 expression levels compared with YP^WT. Conclusions: Collectively, these findings demonstrate that YPR1 plays a crucial role in bacterial blight resistance in common wild rice. As a novel CNL-type NLR gene conferring specific resistance to multiple Xoo strains, YPR1 provides a promising genetic resource for the molecular breeding of BB-resistant rice varieties. Full article

Backgrounds: Accurate annotation of open reading frames (ORFs) is fundamental for understanding gene function and post-transcriptional regulation. A critical but often overlooked aspect of transcriptome annotation is the selection of authentic translation start sites. Many genome annotation pipelines identify the longest possible ORF in alternatively spliced transcripts, using internal methionine codons as putative start sites. However, this computational approach ignores the biological reality that ribosomes select start codons based on sequence context, not ORF length. Methods: Here, we demonstrate that this practice leads to systematic misannotation of nonsense-mediated decay (NMD) targets in the Arabidopsis thaliana Araport11 reference transcriptome. Using TranSuite software to identify authentic start codons, we reanalyzed transcriptomic data from an NMD-deficient mutant. Results: We found that correct ORF annotation more than doubles the number of identifiable NMD targets with premature termination codons followed by downstream exon junctions, from 203 to 426 transcripts. Furthermore, we show that incorrect ORF annotations can lead to erroneous protein structure predictions, potentially introducing computational artefacts into protein databases. Conclusions: Our findings underscore the importance of biologically informed ORF annotation for accurate assessment of post-transcriptional regulation and proteome prediction, with implications for all eukaryotic genome annotation projects. Full article

Formaldehyde (FA) is commonly used for hatchery disinfection, where it reduces microbial growth, ensures successful egg hatch and enhances healthy production, but its specific effects on embryonic development remain unclear. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and may mediate FA-induced transcriptional responses. Here, we investigated the impact of FA treatment on miRNA profiles in chicken embryo liver. Small RNA-seq libraries were constructed and sequenced using the Illumina NextSeq platform. Reads were trimmed and quantified using miRDeep2 version 2.0.0.3. Differential expression analysis was performed with DESeq2 (p-adjusted < 0.05 and |log₂FC| > 1). Target genes of differentially expressed miRNAs (DEMs) were predicted with miRDB, and GO/KEGG/Reactome enrichment was conducted. Out of 662 total mature miRNAs detected, differential expression analysis identified 30 DEMs (11 up-regulated, 19 down-regulated). The highest fold increase was determined for gga-miR-3533 (log₂FC = 4.45), and the most significant decrease was determined for gga-miR-133b (log₂FC = −3.38). Pathway analysis revealed miRNAs affecting signaling pathways along with modules related to post-translational protein modification, immune system, and oxidative stress pathways. Our study demonstrates that FA treatment can affect critical biological processes by altering miRNA-mediated regulation in the developing embryonic liver and point to the need for functional validation of miRNA-target interactions to help determine mechanisms for FA benefits. Long term, these data may help serve as reference to identify new treatments with optimized response profiles. Full article