Search Results (7,207)

During pregnancy, the regulation of autophagy and ferroptosis dynamically supports placental development and fetal health. Both processes—autophagy, clearing damaged organelles to maintain placental function, and ferroptosis, driven by iron-dependent lipid peroxidation—are involved in pathological conditions such as preeclampsia. Emerging evidence suggests that gut microbiota-derived metabolites act as key regulators of this balance, yet their specific roles across different trimesters remain unclear. This review compiles evidence on how gut microbiota metabolites, like short-chain fatty acids and trimethylamine N-oxide, serve as trimester-specific modulators of the autophagy–ferroptosis balance during pregnancy. We explain how these metabolites influence pregnancy outcomes by regulating placental autophagy and ferroptosis. Furthermore, we explore potential diagnostic and therapeutic approaches for pregnancy complications, focusing on metabolite-based biomarkers and interventions that target microbial–metabolic interactions. Full article

Histone post-translational modifications (PTMs) have emerged as promising epigenetic biomarkers with increasing forensic relevance. Unlike conventional genetic markers such as short tandem repeats (STRs), histone modifications can offer additional layers of biological information, capturing individual-specific regulatory states and remaining detectable even in degraded forensic samples. This review highlights recent advances in understanding histone PTMs in forensic contexts, focusing on three key domains: analysis of degraded biological evidence, differentiation of monozygotic (MZ) twins, and postmortem interval (PMI) estimation. We summarize experimental findings from human cadavers, animal models, and typical forensic samples including bone, blood, and muscle, illustrating the stability and diagnostic potential of marks such as H3K4me3, H3K27me3, and γ-H2AX. Emerging technologies including CUT&Tag, MALDI imaging, and nanopore-based sequencing offer novel opportunities to profile histone modifications at high resolution and low input. Despite technical challenges, these findings support the feasibility of histone-based biomarkers as complementary tools for forensic identification and temporal analysis. Future work should prioritize methodological standardization, inter-laboratory validation, and integration into forensic workflows. However, the forensic applicability of these modifications remains largely unvalidated, and further studies are required to assess their reliability in casework contexts. Full article

Motor Neuron Diseases (MNDs) such as Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Hereditary Spastic Paraplegia (HSP), Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), Multisystem Proteinopathy (MSP), Spinal and Bulbar Muscular Atrophy (SBMA), and ALS associated to Frontotemporal Dementia (ALS-FTD), have traditionally been studied as distinct entities, each one with unique genetic and clinical characteristics. However, emerging research reveals that these seemingly disparate conditions converge on shared molecular mechanisms that drive progressive neuroaxonal degeneration. This narrative review addresses a critical gap in the field by synthesizing the most recent findings into a comprehensive, cross-disease mechanisms framework. By integrating insights into RNA dysregulation, protein misfolding, mitochondrial dysfunction, DNA damage, kinase signaling, axonal transport failure, and immune activation, we highlight how these converging pathways create a common pathogenic landscape across MNDs. Importantly, this perspective not only reframes MNDs as interconnected neurodegenerative models but also identifies shared therapeutic targets and emerging strategies, including antisense oligonucleotides, autophagy modulators, kinase inhibitors, and immunotherapies that transcend individual disease boundaries. The diagnostic and prognostic potential of Neurofilament Light Chain (NfL) biomarkers is also emphasized. By shifting focus from gene-specific to mechanism-based approaches, this paper offers a much-needed roadmap for advancing both research and clinical management in MNDs, paving the way for cross-disease therapeutic innovations. Full article

Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising plasma proteomics, post-translational modifications (PTMs), and metabolomics to systematically dissect SCZ pathophysiology. In a cohort of 104 individuals, comparative analysis of 17 machine learning models revealed that multi-omics integration significantly enhanced classification performance, reaching a maximum AUC of 0.9727 (95% CI: 0.8889–1.000) using LightGBMXT, compared to 0.9636 (95% CI: 0.8636–1.0000) with CNNBiLSTM for proteomics alone. Interpretable feature prioritization identified carbamylation at immunoglobulin-constant region sites IGKC_K20 and IGHG1_K8, alongside oxidation of coagulation factor F10 at residue M8, as key discriminative molecular events. Functional analyses identified significantly enriched pathways including complement activation, platelet signaling, and gut microbiota-associated metabolism. Protein interaction networks further implicated coagulation factors F2, F10, and PLG, as well as complement regulators CFI and C9, as central molecular hubs. The clustering of these molecules highlights a potential axis linking immune activation, blood coagulation, and tissue homeostasis, biological domains increasingly recognized in psychiatric disorders. These results implicate immune–thrombotic dysregulation as a critical component of SCZ pathology, with PTMs of immune proteins serving as quantifiable disease indicators. Our work delineates a robust computational strategy for multi-omics integration into psychiatric research, offering biomarker candidates that warrant further validation for diagnostic and therapeutic applications. Full article

Depression represents one of the most prevalent mental health disorders globally, significantly impacting quality of life and posing substantial healthcare challenges. Traditional diagnostic methods rely on subjective assessments and clinical interviews, often leading to misdiagnosis, delayed treatment, and suboptimal outcomes. Recent advances in biosensing technologies offer promising avenues for objective depression assessment through detection of relevant biomarkers and physiological parameters. This review examines multi-modal biosensing approaches for depression by analyzing electrochemical biosensors for neurotransmitter monitoring alongside wearable sensors tracking autonomic, neural, and behavioral parameters. We explore sensor fusion methodologies, temporal dynamics analysis, and context-aware frameworks that enhance monitoring accuracy through complementary data streams. The review discusses clinical validation across diagnostic, screening, and treatment applications, identifying performance metrics, implementation challenges, and ethical considerations. We outline technical barriers, user acceptance factors, and data privacy concerns while presenting a development roadmap for personalized, continuous monitoring solutions. This integrative approach holds significant potential to revolutionize depression care by enabling earlier detection, precise diagnosis, tailored treatment, and sensitive monitoring guided by objective biosignatures. Successful implementation requires interdisciplinary collaboration among engineers, clinicians, data scientists, and end-users to balance technical sophistication with practical usability across diverse healthcare contexts. Full article

Sjögren’s Disease (SjD) is an autoimmune disorder characterized by sicca symptoms arising from impaired salivary and lacrimal gland function and accompanying extraglandular involvement. SjD is recognized as an illness of female dominance for which the 2002 American–European Consensus Group Classification Criteria and the American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 classification criteria are utilized for inclusion in clinical trials, and treatment recommendations from countries belonging to the American College of Rheumatology or the European Alliance of Associations for Rheumatology are globally recognized. It is presumed that there are geographical differences among female sufferers, and unique diagnostic criteria and recommendations are used in clinical practice in Japan. In addition to the items included in the classification criteria, several methods to measure saliva secretion, serum biomarkers, and artificial intelligence tools have recently been reported to be useful for the assessment of SjD. While symptomatic therapies including tear drops, artificial saliva, and muscarinic agonists are still the mainstay for treating SjD, several kinds of molecular targeted drugs, such as biological drugs and Janus kinase inhibitors, that are expected to improve the prognosis of SjD have been tested in recent clinical trials. Full article

Intravascular biosensors have become a crucial and novel class of devices in healthcare, enabling the constant real-time monitoring of essential physiological parameters directly within the circulatory system. Recent developments in micro- and nanotechnology have relevantly improved the sensitivity, miniaturization, and biocompatibility of these devices, thereby enabling their application in precision medicine. This review summarizes the latest advances in intravascular biosensor technologies, with a special focus on glucose and oxygen level monitoring, blood pressure and heart rate assessment, and early disease diagnostics, as well as modern approaches to drug therapy monitoring and delivery systems. Key challenges such as long-term biostability, signal accuracy, and regulatory approval processes are critical considerations. Innovative strategies, including biodegradable implants, nanomaterial-functionalized surfaces, and integration with artificial intelligence, are regarded as promising avenues to overcome current limitations. This review provides a comprehensive roadmap for upcoming research and the clinical translation of advanced intravascular biosensors with a strong emphasis on their transformative impact on personalized healthcare. Full article

Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on the healthcare systems. Thus, a number of novel technological approaches have emerged in order to face some of the pivotal questions still associated with IBD. In navigating the intricate landscape of IBD, biosensors act as indispensable allies, bridging the gap between traditional diagnostic methods and the evolving demands of precision medicine. Continuous progress in biosensor technology holds the key to transformative breakthroughs in IBD management, offering more effective and patient-centric healthcare solutions considering the One Health Approach. Here, we will delve into the landscape of biomarkers utilized in the diagnosis, monitoring, and management of IBD. From well-established serological and fecal markers to emerging genetic and epigenetic markers, we will explore the role of these biomarkers in aiding clinical decision-making and predicting treatment response. Additionally, we will discuss the potential of novel biomarkers currently under investigation to further refine disease stratification and personalized therapeutic approaches in IBD. By elucidating the utility of biosensors across the spectrum of IBD care, we aim to highlight their importance as valuable tools in optimizing patient outcomes and reducing healthcare costs. Full article

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Background and Objectives: The worldwide incidence of renal cell carcinoma (RCC) rose by 22% between 2012 and 2022. In Australia, RCC accounted for 2.8% of all cancer diagnoses and contributing to 1.8% of cancer-related deaths. Identification of RCC biomarkers may aid in diagnosis and management. Methods: A systematic review of immunohistochemical markers of RCC studies published between 1990 and 2019 was undertaken to select candidate biomarkers of RCC. Immunohistochemical staining of 73 clear cell RCC tumors and paired normal tissue was undertaken using selected markers. Semi-quantitative and quantitative analysis of staining intensity between paired samples was undertaken to evaluate utility as potential biomarkers, using Chi-square tests and paired t-tests for analysis. As an exploratory analysis, staining intensity was also compared on clinical/demographic variables using linear and logistic regression. Results: There were 123 candidate biomarkers identified in 91 studies. Four candidate markers were selected for further investigation: aminopeptidase A (APA)/cluster of differentiation (CD)249, aminopeptidase N (APN)/CD13, gamma-glutamyl transferase (GGT), and neuron-specific enolase (NSE). APA, GGT, and APN all demonstrated reduced staining intensity in the tumor compared with normal tissue (p < 0.001 for all). NSE demonstrated a statistically significant increase in expression in tumor compared with normal tissue (p < 0.001), and this was more pronounced in patients aged >60 years (p = 0.038). Conclusions: The utility of APA, APN, and GGT as diagnostic biomarkers in clear cell RCC is limited. NSE may have some role as a biomarker for clear cell RCC, particularly among older patients; however, further investigation is required. Full article

Multiple sclerosis (MS), a chronic disease of the central nervous system, is known to cause structural and vascular changes in the retina. Although optical coherence tomography (OCT) and fundus photography can detect retinal thinning and circulatory abnormalities, these findings are not specific to MS. This study explores the potential of Infrared Scanning-Laser-Ophthalmoscopy (IR-SLO) imaging to uncover vascular morphological features that may serve as MS-specific biomarkers. Using an age-matched, subject-wise stratified k-fold cross-validation approach, a deep learning model originally designed for color fundus images was adapted to segment optic disc, optic cup, and retinal vessels in IR-SLO images, achieving Dice coefficients of 91%, 94.5%, and 97%, respectively. This process included tailored pre- and post-processing steps to optimize segmentation accuracy. Subsequently, clinically relevant features were extracted. Statistical analyses followed by SHapley Additive exPlanations (SHAP) identified vessel fractal dimension, vessel density in zones B and C (circular regions extending 0.5–1 and 0.5–2 optic disc diameters from the optic disc margin, respectively), along with vessel intensity and width, as key differentiators between MS patients and healthy controls. These findings suggest that IR-SLO can non-invasively detect retinal vascular biomarkers that may serve as additional or alternative diagnostic markers for MS diagnosis, complementing current invasive procedures. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation. Full article

Immunoglobulin light chains are essential components of intact immunoglobulins, traditionally believed to be produced exclusively by B cells. Physiologically, excess light chains not assembled into intact antibodies exist as free light chains (FLCs). Increasingly recognized as important biomarkers for diseases such as multiple myeloma, systemic amyloidosis, and light chain-related renal injuries, FLCs have also been shown in recent decades to originate from non-B cell sources, including epithelial and carcinoma cells. This review primarily focuses on novel non-B cell-derived FLCs, which challenge the conventional paradigms. It systematically compares B cell-derived and non-B cell-derived FLCs, analyzing differences in genetic features, physicochemical properties, and functional roles in both health and disease. By elucidating the distinctions and similarities in their nature as immune regulators and disease mediators, we highlight the significant clinical potential of FLCs, particularly non-B cell-derived FLCs, for novel diagnostic and therapeutic strategies. Full article