Search Results (1,472)

For decades, peritoneal metastases (PM) have been regarded as a terminal manifestation of advanced malignancies and managed primarily with palliative intent because of limited sensitivity to systemic therapies. Accumulating clinical, molecular, and immunological evidence now supports the view that PM is not merely an anatomic pattern of spread but a distinct metastatic niche with characteristic biological, microenvironmental, and therapeutic features. This review summarizes the major routes of PM development—transcoelomic, lymphatic, and hematologic dissemination—and emphasizes how these pathways converge through shared biological programs. Core mechanisms include epithelial–mesenchymal transition (EMT), adhesion signaling, extracellular matrix remodeling, and tumor–immune cell interactions. A central focus is the peritoneal tumor microenvironment: mesothelial-to-mesenchymal transition, cancer-associated fibroblast activity, adipocyte-derived metabolic support, macrophage polarization, and regulatory T-cell enrichment collectively shape an immunotolerant and treatment-resistant niche on the peritoneal surface. In addition, evidence from pre-metastatic niche biology suggests that primary tumor-derived exosomes and epitranscriptomic regulation can prime the peritoneal environment before overt implantation. These features provide a biological rationale for locoregional strategies such as cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, as well as emerging intraperitoneal modalities and microenvironment-targeted approaches. Finally, organoid platforms, liquid biopsy-based minimal residual disease monitoring, and theranostic technologies may enable more personalized, biology-driven management of PM. Full article

Background/Objectives: Antibody–drug conjugates (ADCs) have transformed the therapeutic landscape of breast cancer, expanding treatment opportunities across multiple disease settings. However, their increasing clinical use has revealed a heterogeneous spectrum of toxicities that extends beyond conventional chemotherapy-related adverse events. Emerging evidence suggests that ADC-associated toxicities are driven by a complex interplay between ADC structural characteristics, including target antigen expression, payload properties, linker stability, drug-to-antibody ratio, and patient-related susceptibility factors. This review aims to provide a comprehensive overview of ADC-related toxicities in breast cancer, integrating mechanistic insights with clinical management strategies and risk-adapted approaches. Methods: A narrative review of the literature was conducted focusing on clinical trials, real-world studies, translational investigations, and mechanistic evidence related to ADC-associated toxicities in breast cancer. Particular attention was given to the relationship between ADC design, toxicity mechanisms, patient-specific risk factors, and clinical management. Results: ADC-related toxicities encompass a broad range of adverse events, including hematologic toxicity, interstitial lung disease, gastrointestinal complications, hepatotoxicity, peripheral neuropathy, stomatitis, ocular toxicity, dermatologic adverse events, and cardiovascular manifestations. Current evidence indicates that toxicity profiles differ substantially across ADCs and are influenced by multiple factors, including payload class, linker chemistry, target biology, intracellular trafficking, bystander effects, systemic payload exposure, and host-related characteristics. While several toxicities can be anticipated through careful monitoring and early intervention, clinically significant variability remains, and validated predictive biomarkers are largely lacking. Emerging real-world evidence further highlights the importance of individualized toxicity assessment and multidisciplinary management. Conclusions: ADC-related toxicity should be viewed as a multifactorial biological process resulting from the interaction between ADC design and host susceptibility rather than as a uniform class effect. A mechanistic understanding of toxicity pathways may improve risk stratification, toxicity monitoring, and personalized management strategies. Future research should focus on the development of predictive biomarkers, pharmacologic risk models, and next-generation ADC platforms with improved therapeutic indices. This review proposes an integrated framework linking ADC structural determinants, toxicity mechanisms, and clinical management to support safer and more individualized use of ADCs in breast cancer. Full article

The carcinogenic liver fluke Opisthorchis viverrini underlies one of the world’s heaviest burdens of bile duct cancer, yet for decades it was treated as a single, genetically uniform parasite whose transmission was shaped mainly by environment and human behavior. However, advances in molecular biology have fundamentally reshaped this conceptual model. Evidence accumulated over the past three decades demonstrates that O. viverrini comprises geographically structured populations linked to hydrological connectivity, host distribution, and long-term evolutionary processes across interconnected river systems of mainland Southeast Asia, particularly within the Lower Mekong Basin. This review synthesizes research on the systematics and population structure of O. viverrini and its Bithynia snail hosts, tracing the transition from early allozyme studies to contemporary DNA-based and genomic approaches. Collectively, mitochondrial, nuclear, microsatellite, and intron markers reveal strong spatial structuring among parasite populations, while genetic patterns observed in snail hosts show partial geographic concordance with parasite population structure, suggesting that both may be influenced by shared hydrological organization, ecological isolation, and host connectivity across endemic aquatic systems. Population structure is strongly scale-dependent, with local panmixia often occurring within connected aquatic systems but pronounced differentiation emerging across broader geographic regions. Together, these findings indicate that transmission dynamics are shaped not only by environmental and behavioral factors, but also by evolutionary and landscape-level processes influencing host and parasite connectivity. Finally, we emphasize the increasing significance of population genomics and landscape genetics in understanding how transmission systems persist, disperse, reconnect, and respond to environmental change across endemic landscapes. Full article

Postoperative wound complications remain a major cause of morbidity, prolonged hospitalization, increased healthcare costs, and reduced quality of life. While traditional wound dressings functioned primarily as passive barriers against contamination and exudate, advances in wound biology have transformed surgical wound management. Tissue repair is now recognized as a dynamic immunometabolic process involving coordinated interactions among immune cells, stromal populations, extracellular matrix remodeling, mechanotransduction, mitochondrial function, redox balance, microbial ecology, and bioelectrical signaling. Consequently, modern wound dressings are increasingly designed as bioactive systems capable of actively modulating the wound microenvironment. Recent developments in biomaterials science, immunoengineering, nanotechnology, extracellular vesicle biology, bioelectronics, and artificial intelligence have enabled the creation of advanced wound platforms, including stimuli-responsive hydrogels, immunomodulatory biomaterials, nanozyme-based dressings, conductive scaffolds, oxygen-generating matrices, extracellular vesicle-loaded systems, and biosensor-integrated interfaces. Therapeutic strategies are progressively shifting from antimicrobial-focused approaches toward immune-regenerative modulation targeting chronic inflammation, mitochondrial dysfunction, ferroptosis, cellular senescence, and impaired mechanobiological signaling. This review examines emerging surgical wound dressings from mechanistic, translational, and biomaterial perspectives, highlighting current innovations, translational challenges, and future directions. Collectively, these technologies may enable intelligent therapeutic systems capable of sensing and directing tissue regeneration in real time. Full article

Background/Objectives: Identifying aggressive tumor biology within early-stage hepatocellular carcinoma (HCC) remains challenging. Scores based on liver function, systemic inflammation, and HCC biomarkers have been linked to overall survival prognosis; however, the combined ability of these scores to assess tumor-specific prognosis in early-stage disease is unclear. In this single-center, prospective study, biomarker profiling with AFP, AFP-L3, and DCP, along with modified albumin–bilirubin (mALBI), and neutrophil–lymphocyte ratio (NLR)/platelet–lymphocyte ratios (PLRs) were evaluated to determine their prognostic role in assessing clinical manifestations of aggressive biology by stratifying HCC progression risk. Methods: Indices and biomarkers were assessed at BCLC-A-stage HCC diagnosis and prior to liver-directed therapy (LDT). The primary prospective study endpoint was time-to-advanced-stage tumor progression (TTP). Results: The cohort included 232 patients diagnosed with early-stage HCC who underwent treatment with LDT. A multivariate model revealed that mALBI grade (p = 0.021), cumulative lesion size (p = 0.005), and elevations in HCC biomarkers (p < 0.001) were associated with TTP. Biomarker profile stratified TTP (p < 0.001) in which patients with complex profiles (3+) had 1-year progression risks of 69%. The biomarker system retained the ability to stratify TTP within small (≤3 cm) and large (>3 cm) cumulative tumor burden (p < 0.001, p = 0.005). While PLR was not prognostic for TTP, NLR disappeared from the multivariate model and mALBI stratified long-term progression risk (p = 0.003). In low-complex biomarker patients (0–1+), mALBI stratified progression risk (p = 0.001). Conclusions: Multi-positive biomarker profiling in early-stage HCC identifies a population with clinical manifestations of aggressive tumor biology at high risk of rapid post-treatment disease progression that may benefit from more aggressive treatment approaches. In patients with low-risk biomarker profiles (0–1+), mALBI can assess longer-term (>1-year) post-treatment disease progression risk, while scores based on systemic inflammation were not associated with tumor-restricted outcomes. Full article

Stroke remains one of the leading causes of long-term disability and death worldwide. Growing evidence suggests that both stroke onset and severity exhibit strong circadian patterns. This blood–brain interface (BBI), which regulates bidirectional communication between the peripheral circulation and the central nervous system, plays a critical role in cerebrovascular injury. Aging further exacerbates these processes by dampening the molecular clock function and increasing inflammatory activation. In this review, we examine the circadian regulation of the BBI, aging, and its implications in stroke vulnerability. Understanding how circadian biology modulates neurovascular function may reveal novel therapeutic targets and time-of-day-dependent approaches for stroke prevention and treatment. Full article

Antimicrobial resistance and persistent biofilm-associated infections have renewed interest in bacteriophages as alternatives or complements to conventional antibiotics. However, broader therapeutic adoption remains constrained by slow phage discovery, incomplete genome characterization, narrow host range, complex therapeutic matching, and manufacturing variability. Artificial intelligence (AI) offers computational approaches that may help address several of these limitations. This comprehensive narrative review discusses current AI applications across the bacteriophage pipeline, including metagenomic phage discovery, genome annotation, phage–host interaction prediction, personalized phage selection, cocktail optimization, and phage–antibiotic combination design. The review also examines AI-assisted synthetic biology approaches, including receptor-binding protein redesign, CRISPR-enabled engineering, generative genome design, and biosafety screening, as well as emerging applications in bioprocess optimization, yield prediction, purification analytics, quality assurance, and supply-chain management. Current evidence suggests that AI may accelerate phage identification, improve host-range prediction, support therapeutic optimization, and strengthen manufacturing consistency, potentially facilitating the transition of phage therapy from individualized rescue interventions toward more scalable antimicrobial platforms. Nevertheless, major limitations remain, including fragmented, taxonomically biased datasets; limited external validation; restricted interpretability; privacy concerns; biosafety oversight; and evolving regulatory frameworks. Future progress will depend on standardized datasets, multimodal validation, scalable manufacturing systems, experimental and clinical verification, and coordinated regulatory development. Full article

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation and survival of neoplastic plasma cells (PCs) within the bone marrow (BM), where disease progression is critically supported by interactions with the BM tumor microenvironment (TME). Despite significant advances in therapeutic strategies, MM remains incurable, underscoring the need for improved preclinical models to better understand the disease biology and therapeutic response. This review summarizes current and emerging MM treatment approaches and critically examines the development of models designed to more accurately recapitulate interactions between MM-PCs and the surrounding BM niche. We describe established and emerging modeling platforms, with emphasis on advanced three-dimensional (3D) culture systems and highlight their unique contributions to the preclinical assessment of both existing and novel therapies. The advantages of 3D models, including in vitro and in silico systems, over traditional two-dimensional (2D) models are discussed, alongside a comparative evaluation of scaffold-free and scaffold-based approaches. In addition, the benefits and recent advances in the customization of BM niche simulation using microfluidic technologies and organ-on-a-chip platforms are reviewed. The application of 3D models in MM research is increasingly enabling the study of disease pathogenesis, progression, drug resistance and precision-medicine approaches (informed by biomarker discovery). Although standardized preclinical approaches for evaluating MM therapeutics are currently lacking, the growing imperative to reduce reliance on preclinical animal models highlights the importance of alternate systems. Consequently, the development and adoption of physiologically relevant models that accurately recapitulate MM-PC interactions with the BM TME will be critical for advancing future therapeutic strategies in MM. Full article

CRISPR-Cas9 has transformed microbial biotechnology by enabling precise genome modifications; however, achieving high editing efficiency remains a challenge due to multiple determinants, including on-target specificity, off-target events, PAM sequence, sgRNA scaffold composition, and RNA secondary structure. Our review foresees how artificial intelligence (AI) can address those challenges by enabling automated identification as well as highly active guide RNA (gRNA) optimisation. We highlight the influence of a data-driven training strategy that is focused on high-quality, diverse, and accurately labelled microbial datasets—mainly, given the limitations of models derived from mammalian systems that are not directly transferable to microbial organisms. Moreover, we discuss the key role of FAIR (Findable, Accessible, Interoperable, and Reusable) data principles and centralised, curated CRISPR-Cas databases as foundational elements for developing robust and predictive frameworks. Emerging directions are also explored, including generative AI approaches capable of supporting automated experimental planning. By considering the potential dual use of such technologies, the review further addresses bioethical considerations and regulatory frameworks necessary to ensure responsible genome engineering as a milestone, as well as the implementation of safeguards against misuse, particularly in pathogenic microorganisms. Furthermore, the convergence of standardised experimental data, specialised microbial datasets, and advanced AI architectures is paving the way to transform microbial biotechnology by accelerating metabolic engineering and synthetic biology applications. Full article

Adipose tissue remodeling is a dynamic process essential for metabolic homeostasis, enabling tissue expansion, extracellular matrix (ECM) turnover, angiogenesis, and coordinated immune adaptation. In obesity, however, maladaptive remodeling characterized by fibrosis, chronic low-grade inflammation, and hypoxia disrupts adipose plasticity and promotes systemic insulin resistance. Central to these processes is the tightly regulated homeostasis between proteases and their inhibitors, in which the serine protease inhibitor (serpin) superfamily represents an important yet underappreciated regulatory axis. Beyond their classical roles in coagulation and fibrinolysis, serpins regulate ECM remodeling, macrophage recruitment and polarization, cytokine signaling, angiogenic responses, adipokine activity, and insulin sensitivity, thereby orchestrating immune–metabolic crosstalk within adipose depots. Emerging evidence indicates that individual serpins exert distinct and context-dependent effects, with some promoting fibrosis, inflammation, and metabolic dysfunction, whereas others preserve adipose tissue homeostasis and metabolic function. This review synthesizes current knowledge on the structural and functional diversity of the serpin superfamily and examines their mechanistic roles in adipose tissue remodeling during obesity, with particular emphasis on how adipose-associated serpins regulate adipose tissue homeostasis, depot-specific remodeling, and immune–metabolic crosstalk. The review further discusses the experimental and translational applications of emerging single-cell and spatial transcriptomics, multi-omics, and computational approaches that may advance the understanding of serpin biology, improve the investigation of human adipose tissue, and accelerate the identification of clinically relevant serpin-related biomarkers and therapeutic targets for obesity and related metabolic disorders. By positioning serpins as key regulators of adipose tissue remodeling and immune–metabolic integration, this review highlights protease–antiprotease balance as a central determinant of metabolic health and identifies serpins as promising biomarkers and therapeutic targets for obesity and related metabolic disorders. Full article

Fatty acid-binding protein 7 (FABP7) is a multifunctional lipid chaperone that is enriched in radial glia and astrocytes within the central nervous system (CNS) and is frequently upregulated in glioma. Beyond its established roles in glial development, lipid homeostasis, and circadian regulation, growing evidence positions FABP7 at the intersection of tumor metabolism, neuronal activity, and immune modulation in the brain. In this review, we integrate the physiological functions of FABP7 in glial cells with its tumor-intrinsic and microenvironmental roles in glioma. We summarize how gliomas co-opt FABP7-dependent metabolic, transcriptional, and post-transcriptional programs to promote stemness, lipid remodeling (e.g., altered fatty acid composition, lipid droplet formation, and lipid peroxidation resistance), inflammatory signaling, and invasive growth, including nuclear FABP7-mediated transcriptional activation linked to oncogene status. Furthermore, we discuss the role of FABP7 in shaping the tumor–neuro–immune interface, including regulating immunosuppressive gene networks, pro-tumoral macrophage polarization, resistance to T-cell-induced ferroptosis and immunotherapy, and tumor microtube-mediated integration into neuronal circuits to support glioma progression. Finally, we highlight therapeutic opportunities and challenges, including small-molecule FABP7 inhibitors, brain-directed delivery strategies, chronotherapeutic considerations, and combination approaches with immunotherapy. Collectively, this work positions FABP7-centered metabolic, circadian, and neuro-immune networks as potential vulnerabilities in glioma, linking fundamental glial biology to glioma therapeutics. Full article

High-throughput omics technologies have profoundly transformed our approach to studying biological systems, enabling system-level exploration of genomes, transcriptomes, proteomes, metabolomes, and beyond. Despite these advances, current omics approaches remain limited in capturing dynamic temporal changes, preserving spatial organization within tissues, and effectively integrating multi-layered datasets into coherent biological interpretations. The aim of this review is to provide a structured and critical overview of established, emerging, and conceptual omics sciences, and to propose a unifying framework that expands the boundaries of systems biology. This review organizes established and emerging omics into a structured framework, highlighting conceptual innovations such as adaptomics, resiliomics, chrono-adaptomics, and signalomics. We discuss technological advances, computational strategies, and potential applications for research and clinical practice. Full article

Diabetes mellitus represents a major global health challenge with rapidly increasing prevalence and substantial morbidity driven by metabolic and vascular complications. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and are increasingly implicated in the pathogenesis and progression of diabetes. This review summarizes current knowledge on EV biology, including their classification, cellular sources, biogenesis, uptake mechanisms, and molecular cargo. We discuss the contribution of EV-associated microRNAs to immune dysregulation and β-cell damage in type 1 diabetes mellitus (T1DM), as well as the role of EVs in insulin resistance, metabolic signaling, and vascular dysfunction in type 2 diabetes mellitus (T2DM). Particular emphasis is placed on EV-mediated modulation of endothelial function, angiogenesis, and tissue repair, alongside their involvement in the impairment of insulin receptor integrity. We further explore how lifestyle factors may influence EV composition and function, highlighting their potential integration into preventive strategies. Finally, we evaluate the emerging therapeutic potential of EVs as biomarkers and delivery systems, while addressing current limitations and future directions. Collectively, EVs represent a promising frontier in understanding diabetes pathophysiology and developing innovative diagnostic and therapeutic approaches. Unlike previous reviews that examine EVs separately as biomarkers or therapeutic vehicles, this review integrates emerging evidence supporting EVs as mediators of systemic communication linking pancreatic islets, adipose tissue, immune cells, vascular endothelium, kidney, heart, and retina throughout diabetes progression. We further critically evaluate translational barriers that currently limit clinical implementation of EV-based diagnostics and therapeutics. Full article

The discovery of various CRISPR–Cas systems has revolutionized genome engineering by enabling precise and programmable nucleic acid targeting. Continued exploration of CRISPR diversity, together with advances in computational modeling and deep learning (DL)-based design, has expanded the potential to manipulate nearly any genomic locus, thereby accelerating both basic research and therapeutic applications. This review systematically provides a structured and up-to-date overview of CRISPR–Cas technologies, including their classification, computational modeling strategies, and the integration of machine learning (ML) and DL approaches to predict guide RNA (gRNA) efficiency and specificity. The emphasis is placed on studies published between 2019 and 2025, which highlight significant progress in modeling Cas–gRNA–DNA interactions, optimizing on/off-target prediction, and developing comprehensive CRISPR-related datasets. By synthesizing recent developments in CRISPR biology, computational simulations, and artificial intelligence, this review underscores the importance of interdisciplinary integration to improve the accuracy, safety, and scalability of next-generation genome-editing systems. Full article

Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive and heterogeneous malignancies worldwide, characterized by high rates of locoregional recurrence, metastatic dissemination, and therapeutic resistance. Angiogenesis plays a central role in tumor progression by supporting vascular remodeling, hypoxia adaptation, invasion, immune evasion, and metastatic spread. In HNSCC, angiogenic activation is regulated through complex interactions involving hypoxia-inducible factors, vascular endothelial growth factor (VEGF) signaling, stromal remodeling, inflammatory pathways, and epigenetic mechanisms within the tumor microenvironment. Recent evidence has also highlighted the role of non-coding RNAs, particularly microRNAs, and exosome-mediated communication in modulating angiogenic and immune-related signaling pathways. Although antiangiogenic therapies, including monoclonal antibodies and tyrosine kinase inhibitors, have demonstrated biological activity in HNSCC, their clinical efficacy remains limited by tumor heterogeneity, adaptive resistance mechanisms, toxicity, and the lack of validated predictive biomarkers. Several emerging therapeutic strategies are under preclinical or early clinical investigation in HNSCC, including miRNA-based approaches, nanoparticle-assisted delivery systems, vascular normalization concepts, and combinations with immune checkpoint inhibitors; however, robust clinical evidence for most of these strategies remains limited, and their translation to routine practice requires further validation. This review provides a comprehensive overview of the molecular mechanisms regulating angiogenesis in HNSCC and critically discusses current and emerging pharmacological strategies targeting these pathways. Particular emphasis is placed on VEGF/VEGFR signaling, the integration of miRNA and exosome biology, resistance mechanisms, and translational perspectives for biomarker-guided personalized therapy. The novelty of this review lies in the systematic integration of miRNA- and exosome-mediated angiogenic regulation, therapeutic resistance pathways, and precision medicine strategies into a unified pharmacological framework, addressing gaps not fully covered by prior reviews focused primarily on VEGF-targeted agents. Full article