Search Results (744)

Backgroundand Objectives: Endometrial cancer ranks among the most prevalent gynecologic malignancies in high-income countries, with increasing incidence and mortality driven by the global obesity epidemic. Evidence suggests that women with early-stage disease face a greater risk of death from obesity-related comorbidities than from cancer recurrence and that weight reduction is associated with improvements in quality of life and in the long-term burden of obesity-related morbidity and mortality. Minimally invasive (MIS) metabolic/bariatric surgery is the most effective treatment for achieving significant, sustained weight loss and comorbidities resolution/improvement. Advances in MIS (laparoscopic, robotic, and endoscopic) techniques have reduced perioperative morbidity and mortality. Novel pharmacotherapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), have recently received regulatory approval for weight management and ongoing studies are investigating their therapeutic impact on endometrial carcinogenesis and tumor biology. This review synthesizes and critically appraises evidence on metabolic interventions, including innovative bariatric techniques and pharmacologic agents, with the aim of informing their integration into multidisciplinary, risk-adapted management strategies for patients with severe obesity and endometrial cancer. Materials and Methods: A comprehensive review was conducted in accordance with SANRA (Scale for the Assessment of Narrative Review Articles) criteria. Results: Emerging evidence indicates that MIS metabolic/bariatric surgery combined with hysterectomy is feasible and may be integrated into the multidisciplinary management of selected patients with severe obesity and endometrial hyperplasia or carcinoma. GLP-1RAs may modulate both the obesogenic systemic milieu and selected tumor-associated pathways, although definitive clinical evidence of direct antitumor effect and oncologic benefit in endometrial cancer has not been established. Conclusions: Obesity is a modifiable risk factor for endometrial cancer. Metabolic/bariatric interventions represent a promising component of the comprehensive, patient-centered management of this disease. Prospective studies are essential to clarify the association between these interventions and longitudinal oncologic outcomes, the feasibility and potential benefits of combined approaches, and their differential impact according to the molecular classification of endometrial cancers. Although weight reduction is associated with a lower risk of endometrial cancer, a direct improvement in cancer-specific survival has not yet been demonstrated; weight-loss management therefore represents a promising component of care in the severely obese population, and its incorporation into formal guidelines requires confirmation in prospective studies. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide despite advances in screening, surgical techniques, and systemic therapies. In recent years, exosomes—nanoscale extracellular vesicles involved in intercellular communication—have emerged as critical regulators of CRC biology. Exosomes mediate tumor progression, metastatic dissemination, immune evasion, and therapeutic resistance through the transfer of bioactive molecules including proteins, lipids, and non-coding RNAs. Moreover, exosomes have gained increasing attention as promising liquid biopsy tools and therapeutic platforms due to their stability, biocompatibility, and ability to reflect tumor molecular dynamics. This review provides a comprehensive overview of exosome biogenesis, molecular composition, and their functional roles in CRC pathogenesis. We further discuss their diagnostic and prognostic value, involvement in therapeutic resistance, and emerging therapeutic applications, with particular emphasis on translational and surgical oncology implications. Finally, we highlight current limitations and future perspectives for clinical integration of exosome-based strategies in CRC management. Full article

Macadamia (Macadamia spp.) is an economically important nut crop whose severe recalcitrance to genetic transformation substantially hinders progress in functional genomics and molecular breeding. To overcome this critical technical bottleneck, this study established a highly efficient and broadly applicable in planta hairy root genetic transformation system with integrated visual screening. This system utilizes an Agrobacterium rhizogenes-mediated transformation method, employing multiple visual reporter gene systems (DsRed2, eGFP, RUBY, and AtPAP2) to achieve antibiotic-independent and non-destructive screening of transgenic roots. Notably, the system innovatively incorporates the air layering (marcotting) technique to extend in planta genetic transformation to branches of mature trees in the field. By circumventing the stringent sterile conditions required for conventional in vitro tissue culture, this approach achieves a largely genotype-independent transformation across open-pollinated seedlings with diverse genetic backgrounds (A4, GR1, HAES900, and O.C.). The transgenic hairy root induction frequencies ranged from 39.25% to 47.38%, although the GR1 genotype exhibited a notable developmental stage-dependent decline in transformation efficiency. Furthermore, transgenic hairy roots were successfully induced on mature tree branches, with a maximum induction rate of 28.2%. Gene expression analyses confirmed the stable, high-level expression of the target transgenes in all the transgenic hairy root lines. This in planta transformation system provides a reliable in vivo experimental platform for the rapid functional validation of candidate genes and the investigation of root biology in Macadamia. Moreover, it establishes a novel strategy for plant regeneration via root-to-shoot organogenesis, offering a promising avenue for the genetic improvement of recalcitrant woody plants. Full article

Background: Epigenomics has emerged as an essential field in modern molecular biology, providing a critical layer of gene regulation. DNA methylation, histone modifications and alterations to the chromatin accessibility of DNA have been widely associated with complex diseases including cancer. The most recent developments in high-throughput sequencing technology have made it possible to profile epigenetic landscapes genomically on a large scale. However, bulk averaging can obscure cellular heterogeneity essential for understanding complex disease states. The purpose of the review is to survey accessible tools and algorithms to conduct an Epigenomic study in the field of biomedical research, from bulk tissue analysis to the high-resolution frontier of single-cell epigenomics. Methods: We performed a comparative analysis of common methods used to analyze DNA methylation, chromatin immunoprecipitation, sequencing analysis and chromatin accessibility profiling. We described the standardized bioinformatics tools and pipelines required to transform raw sequencing data into mechanistic biological understanding, highlighting the role of quality control, peak calling, and differential analysis. Furthermore, we explore the integration of epigenomics with other “omics” layers through advanced computational frameworks, including machine learning and network-based modeling. Results: These advanced multi-omics techniques demonstrate promising clinical utility by enabling biomarker discovery, disease subtyping, and identification of novel therapeutic targets. Conclusions: Despite challenges with data complexity, the fusion of Artificial Intelligence (AI) and single-cell technologies will accelerate the transition toward precision medicine. Full article

Molecular clocks use the accumulation of genetic changes to estimate the timing of evolutionary and demographic events. Since their formulation in the 1960s, molecular clocks have evolved from relatively simple strict-rate assumptions into a diverse set of statistical frameworks that include strict, relaxed, local and time-dependent models. In this review, we examine the conceptual basis of molecular-clock inference and the biological, demographic and methodological factors that influence clock estimates. We distinguish mutation rates from substitution rates and discuss how molecular, genomic, life-history, environmental and population-level processes can affect estimated evolutionary rates. We then review the main analytical approaches used to estimate branch lengths and divergence times, including maximum likelihood, Bayesian inference, parsimony-based methods and regression-based techniques; we also focus on the statistical evaluation of clock-like behaviour. Particular attention is given to calibration, as molecular clocks only become informative for absolute time estimation when genetic distances are anchored to an external temporal framework. We review calibration strategies based on fossils, geological and biogeographic events, founder events, ancient sequences, pedigrees, direct mutation-rate estimates, longitudinal sampling, secondary calibrations and externally estimated substitution rates. Finally, we discuss cases in which molecular-clock estimates show concordance or discordance with independent archaeological, palaeontological or epidemiological evidence, as well as cases where apparent agreement may reflect circular reasoning. We argue that molecular clocks remain essential tools for evolutionary biology, but that their reliability depends on explicit model testing, transparent calibration choices and careful interpretation of the results. Full article

Reverse transcription quantitative PCR (RT-qPCR) is one of the most widely used techniques for gene expression analysis in molecular biology. However, the accuracy of relative gene expression quantification largely depends on the stability of the reference genes used for normalization. Sambucus nigra L. (elderberry) is a valuable medicinal and edible plant rich in anthocyanins and other bioactive compounds. Despite its increasing research and application value, no reference genes have been validated for this species. In this study, we applied RT-qPCR alongside four algorithms (GeNorm, NormFinder, BestKeeper, and RefFinder) to assess the expression stability of nine candidate reference genes across ten samples representing five tissue types (including stems, flowers, leaves, roots, fruits) at different developmental stages. The results showed that VAMP and Pol were the most suitable reference gene combination for normalization across different tissues of S. nigra. For studies involving only vegetative tissues (leaves and stems), our results recommend that RPB2 and RPB5 are the most stable and suitable reference genes. This study provides reliable reference genes for accurate RT-qPCR-based gene expression analysis in S. nigra and establishes a useful methodological basis for future functional genomics and molecular breeding studies in this species. Full article

Skeletal muscle serves as the direct executor of movement, and the proliferation and migration capacities of its constituent cells represent the key physiological foundation determining equine endurance and speed. Previous whole-transcriptome analysis has shown that Insulin-like Growth Factor 1 (IGF1) is significantly upregulated in Yili horses following racing and is involved in the PI3K-Akt signaling pathway; however, its specific regulatory mechanism in equine skeletal muscle cells remains unclear. This study utilized primary equine skeletal muscle cells as a model. By constructing an IGF1 overexpression plasmid and screening efficient siRNA interference sequences, we employed RT-qPCR and Western Blot techniques to verify gene expression and the activation level of the PI3K/Akt pathway. Cell Counting Kit-8 (CCK-8) assays were used to detect cell proliferation viability, and cell scratch assays were conducted to evaluate migration capacity, aiming to clarify the regulatory effect of IGF1 on the phenotype and function of equine skeletal muscle cells. Functional experiments demonstrated that IGF1 overexpression significantly promoted the proliferation viability (p < 0.0001) and migration rate (p < 0.0001) of equine skeletal muscle cells, whereas knockdown of IGF1 significantly inhibited these cellular capabilities. Mechanistic studies revealed that IGF1 overexpression significantly increased Akt phosphorylation. Notably, IGF1 exerted its biological functions in conjunction with the activation of the PI3K/Akt signaling pathway. In conclusion, IGF1 enhances cell proliferation and wound-healing capacity of primary equine skeletal muscle cells, which correlates with its ability to activate the PI3K/Akt signaling pathway. This study is the first to reveal the critical role of IGF1 in equine skeletal muscle biology at the cellular level, providing experimental evidence for a deeper understanding of the molecular mechanisms underlying the formation of athletic performance in Yili horses. It also offers novel potential targets for the molecular breeding of sport horses and interventions for injury repair. Full article

Breast cancer remains one of the most prevalent malignancies affecting women worldwide and continues to be a leading cause of cancer-related morbidity and mortality. Patients may present with either localized or advanced disease, with clinical outcomes increasingly influenced by molecular subtype and genetic profile. This review highlights the key genetic factors involved in breast cancer, current diagnostic and therapeutic strategies, and promising emerging approaches that may shape future clinical management. Breast cancer diagnosis typically involves clinical breast examination, imaging techniques such as mammography and ultrasound, and confirmatory biopsies. Genetic mutations in specific genes are strongly linked to the development, progression, and metastasis of the disease. Treatment options for localized breast cancer continue to include surgery (lumpectomy or mastectomy) and radiotherapy, combined with systemic therapies tailored to tumor biology, such as endocrine therapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, and cyclin-dependent kinase (CDK)4/6 inhibitors. For advanced or metastatic breast cancer, recent therapeutic advances include the use of immunotherapy (e.g., immune checkpoint inhibitors), Poly (ADP-ribose) polymerase (PARP) inhibitors for Breast Cancer gene (BRCA)-mutated cancers, antibody–drug conjugates, and novel targeted agents, which have significantly improved patient outcomes in selected populations. Recent findings in breast cancer genetics have highlighted the critical role of germline and somatic mutations, particularly in genes such as BRCA1, BRCA2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and TP53, in driving tumor initiation, progression, and therapeutic response. Molecular profiling and next-generation sequencing technologies have enabled more precise tumor classification and facilitated the development of personalized treatment strategies. Despite these advances, treatment resistance and disease recurrence remain major challenges, particularly in aggressive subtypes such as triple-negative breast cancer. Consequently, ongoing research is exploring alternative and complementary approaches, including nanotechnology-based drug delivery systems, gene editing techniques such as clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9) (CRISPR-Cas9), cancer vaccines, and the integration of traditional and plant-derived compounds. These strategies aim to enhance therapeutic efficacy, reduce systemic toxicity, and overcome resistance mechanisms. Full article

Anisakiasis is caused by ingestion of third-stage larvae (L3) of Anisakis in fish. The last decade has improved our understanding of Anisakis and its clinical manifestations, driven by advancements in high-throughput “omics” techniques and molecular diagnostics. This review summarizes major advancements, focusing on molecular mechanisms underlying its pathogenesis, host–pathogen interactions and novel diagnostic approaches. Taxonomical revisions have refined the Anisakis genus, reclassifying several species into Skrjabinisakis and Peritrachelius. Research has highlighted the critical role of Anisakis extracellular vesicles in modulating host immunity. Significant diagnostic breakthroughs include the use of the IgA/IgG4 ratio and antibody avidity profiling to differentiate gastroallergic anisakiasis from chronic urticaria. Identification of α-Gal epitopes in L3 suggests a novel link to α-Gal syndrome and red meat allergy. Ani s 13 and Ani s 14 have been identified as new major allergens, although Ani s 7 remains the gold standard for serological diagnosis. Modern systems biology is revealing how larvae adapt to their host environments, including thermal stress and glucose availability. Finally, emerging evidence suggests potential links between chronic Anisakis exposure and pathologies like cancer and sepsis. These advancements underscore the necessity of global clinical awareness and the potential for Anisakis-derived molecules as templates for future immunotherapies. Full article

Oxidative stress has emerged as an important component of the complex pathophysiology of inflammatory bowel disease (IBD), where increasing evidence suggests an interaction between redox imbalance, immune activation, epithelial dysfunction, and chronic intestinal inflammation. This structured narrative review critically synthesizes current evidence regarding the biological basis of oxidative stress in IBD, with emphasis on cellular and molecular mechanisms, oxidative biomarkers, therapeutic modulation of redox pathways, and their translational relevance. Current evidence indicates that oxidative stress is associated with immune-cell activation, mitochondrial dysfunction, impairment of epithelial homeostasis, and dysregulation of redox-sensitive signaling pathways. Biomarkers including nitric oxide metabolites, malondialdehyde, myeloperoxidase, total antioxidant capacity, serum thiols, and antioxidant enzymes have demonstrated associations with inflammatory activity, while anti-inflammatory, antioxidant, and dietary interventions have been reported to modulate oxidative biomarkers in selected clinical studies. However, substantial methodological heterogeneity, variability in analytical techniques, and limited prospective validation currently restrict their routine clinical application. Moreover, many mechanistic pathways have been characterized predominantly in experimental models, highlighting the need to distinguish biological plausibility from evidence supporting clinical implementation. Overall, oxidative stress represents a promising area of investigation that may contribute to a better understanding of IBD biology and support future biomarker-guided and precision medicine approaches. Nevertheless, further standardized translational and longitudinal clinical studies are required before oxidative biomarkers and redox-targeted strategies can be integrated into routine patient care. Full article

Chloride (Cl⁻) is an essential micronutrient for plants that supports multiple physiological functions throughout plant growth and development. Its effects are strongly concentration-dependent: low Cl⁻ availability promotes beneficial physiological processes, whereas excessive accumulation can induce cytotoxicity. In plants, the movement of Cl⁻ across plasma and organellar membranes is primarily mediated by three principal channel and transporter families: chloride channels (CLC), aluminum-activated malate transporters (ALMT), and slow anion channel-associated homologs (SLAC/SLAH). These families differ in gating mechanisms, ion selectivity, transport properties, and subcellular localization. This review synthesizes current knowledge of plant chloride transport proteins, with emphasis on their phylogenetic distribution, structural organization, and functional diversification. We summarize their core physiological roles in stomatal regulation, water-use efficiency, nutrient uptake, ion homeostasis, growth modulation, and abiotic stress tolerance. We also discuss how their activities are regulated by post-translational modifications, notably phosphorylation and dephosphorylation, as well as by ion concentrations, pH shifts, and phytohormone signaling. Unlike earlier reviews that primarily focused on individual transporter families or specific stress responses, this work provides an integrated framework linking structure–function relationships with regulatory networks. It also evaluates recent advances in high-resolution structural biology, electrophysiological approaches, and in vivo imaging techniques. Furthermore, we delineate current technical bottlenecks and unresolved questions, such as the molecular determinants of substrate specificity and potential cross-talk among transporter families, and propose future directions for crop improvement. By integrating structural, physiological, and regulatory perspectives, this review aims to serve as a valuable reference and stimulate interdisciplinary research on plant chloride biology. Full article

The sequence of messenger RNA (mRNA) not only determines the protein sequence synthesized by a ribosome but also defines the efficiency of this process. Many antibiotics lethal to bacteria inhibit various stages of translation by targeting ribosomal functional centers. Some antibiotics exhibit specificity not only for particular stages of the ribosomal working cycle but also for specific patterns within mRNA sequences. This review covers a broad range of approaches—including in vivo and in vitro methods, low- and high-throughput techniques such as reporter constructs, characterization of inhibitors of protein synthesis (ChIPS), toeprinting, cryogenic electron microscopy (cryo-EM), protein labeling, and those integrated with next-generation sequencing (NGS) like ribosome profiling with following NGS (Ribo-seq), inverse toeprinting coupled with NGS (iTP-seq), high-throughput toeprinting and NGS (Toe-seq), and ribosome display—used to study the sequence specificity of translation inhibitors, a rapidly evolving field crucial to molecular biology. It presents various methodologies, discusses their applications, and provides a comparative analysis. The fundamental research value of this review lies in establishing standardized experimental selection guidelines for scientists investigating ribosome stalling mechanisms, thereby minimizing trial-and-error costs. Equally important is its applied relevance. The review highlights its translational value in aiding the screening and mechanistic analysis of sequence-specific small-molecule inhibitors. Moreover, understanding the mechanisms underlying protein biosynthesis inhibition and their dependence on particular mRNA sequences could enable the development of selective agents that precisely suppress the synthesis of certain polypeptides, such as proteins from pathogenic bacteria or cancer-associated proteins. Full article

This review examines recent quantum chemical methodologies applied to investigating antibiotic structure and mechanisms of action. The discussion is organised into three sections: (1) enzymatic hydrolysis of the β-lactam ring, (2) interactions of antibiotics with ribosomal subunits and enzyme active sites, and (3) complex formation with metal ions. Each section evaluates how quantum chemical approaches, particularly density functional theory (DFT) and hybrid QM/MM techniques, model molecular processes relevant to antibiotic function, including transition states, electron density analyses, and metal coordination effects on antibacterial activity. Selected studies demonstrate the utility of these methodologies in interpreting experimental data and predicting physicochemical and biological properties of novel compounds. Distinct from previous literature, this review provides a comparative and up-to-date synthesis of quantum chemical methods related to enzymatic mechanisms and metal-based antibiotic systems, emphasising experimental validation strategies and practical guidelines for method selection in antibiotic research. It also identifies areas where quantum chemical modelling can integrate with experimental pharmacology and structural biology to support the rational design of next-generation antimicrobial agents. The review concludes by advocating an interdisciplinary framework combining quantum chemistry, biochemistry, and pharmacology to address antibiotic resistance. The review focuses primarily on antibiotics targeting bacterial cell wall and protein synthesis, particularly β-lactam antibiotics, ribosome-targeting agents, and their interactions with metal ions. Computational methods discussed are mainly limited to DFT, ab initio, and hybrid QM/MM approaches. It does not cover membrane-disrupting antibiotics, antiviral or antifungal agents, machine learning-based prediction methods, or purely molecular dynamics approaches outside a quantum mechanical context. Full article

Primary liver malignancies, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although systemic therapies have advanced substantially, intrahepatic tumor progression, liver failure, and portal hypertension continue to drive adverse outcomes in many patients. Interventional radiology plays a central and expanding role in the multidisciplinary management of these tumors by providing image-guided locoregional therapies for local tumor control, downstaging, bridging transplantation or resection, palliation, and potential survival benefit. This narrative review summarizes current evidence and technical considerations for major locoregional approaches, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization, transarterial radioembolization, endobiliary therapies, stereotactic body radiation therapy, irreversible electroporation, histotripsy, high-intensity focused ultrasound, hepatic arterial infusion, and brachytherapy. Interventional radiology also contributes to preoperative liver optimization through portal vein embolization, liver venous deprivation, lobar radioembolization to induce contralateral hypertrophy, and, in some patients, portal decompression before hepatic resection. For hepatocellular carcinoma, ablation and transarterial therapies are integrated into stage-based treatment algorithms and may provide curative-intent treatment in some patients. In intrahepatic cholangiocarcinoma, locoregional therapies provide meaningful disease control and may prolong survival, particularly when combined with systemic therapy. In combined hepatocellular cholangiocarcinoma, treatment remains individualized because of limited prospective data and heterogeneous tumor biology. Beyond cytoreduction, locoregional therapies can modulate the tumor immune microenvironment through immunogenic cell death, antigen release, cytokine signaling, and vascular remodeling, providing a rationale for combination strategies with immune checkpoint inhibitors, anti-angiogenic agents, and targeted therapies. As treatment paradigms evolve, the future of interventional radiology in primary liver cancer will depend on appropriate patient selection, optimized dosimetry and technique, integration with molecular and immunologic biomarkers, and coordinated multidisciplinary care. Full article

Nitric oxide (NO) is a small, highly reactive gaseous signaling molecule that plays diverse and context-dependent roles in microbial physiology and host–microbe interactions. Over the past decade, increasing evidence has revealed the dual nature of NO as both an antimicrobial effector and a signaling mediator involved in microbial stress responses, metabolism, biofilm dynamics, quorum sensing, virulence regulation, and symbiotic interactions. In microbial systems, NO influences adaptation to environmental stress and contributes to mechanisms associated with persistence and antimicrobial resistance. In host organisms, NO functions as a key component of innate immunity while also participating in beneficial interactions involving rhizobia, mycorrhizal fungi, and probiotic microorganisms. Despite its biological significance, accurate detection and quantification of NO remain challenging because of its transient nature, high reactivity, low physiological concentrations, and interference from related reactive oxygen and nitrogen species. Recent advances in biosensing technologies have substantially improved NO detection capabilities through the development of electrochemical, optical, enzyme-based, microfluidic, wearable, and implantable sensing platforms. These innovations are complemented by analytical techniques including electron paramagnetic resonance spectroscopy, mass spectrometry, fluorescence-based imaging, and advanced microscopy, which enhance sensitivity, specificity, and spatiotemporal resolution in complex biological environments. Concurrently, statistical and computational approaches—including sensor calibration models, multivariate analyses, machine learning algorithms, and bioinformatics pipelines—have become increasingly important for extracting biologically meaningful information from NO-related datasets. Unlike previous reviews that primarily focus on either NO biology or sensing technologies, this review integrates current knowledge of NO-mediated microbial physiology and host–microbe interactions with recent developments in biosensor engineering, analytical methodologies, statistical frameworks, and emerging artificial intelligence (AI)-driven data interpretation. We further highlight applications of NO detection in infectious disease diagnostics, antimicrobial screening, probiotic and biofertilizer evaluation, environmental microbiome monitoring, and real-time studies of symbiosis and infection. Finally, future directions including miniaturized sensing platforms, multi-omics integration, AI-assisted analytics, and sensor standardization are discussed. By unifying molecular, analytical, and computational perspectives, this review provides a multidisciplinary framework and roadmap for advancing NO-based research and translational applications across microbial, environmental, and host-associated systems. Full article