Search Results (72)

Background/Objectives: The relationship between gut microbiota (GM) and microRNAs (miRs) related to lipid metabolism in individuals with metabolic syndrome (MetS) remains unclear. This pilot study examined the relationship between Bacteroidetes and Firmicutes abundance at the phylum level and the plasma levels of miR-122 and miR-370, both of which are associated with lipid metabolism, in Korean individuals with MetS and in healthy controls. We also evaluated the potential of these miRs as biomarkers for MetS. Methods: This study enrolled 7 individuals with MetS and 8 controls. The abundance of GM was analyzed by 16S rRNA amplicon sequencing. To evaluate the relationship between the dominant phyla in the 2 groups, the log ratio of Firmicutes to Bacteroidetes (F/B) was calculated using a centered log-ratio (CLR) transformation. The abundance of the 2 plasma miRs was also quantified by real-time quantitative PCR (RT-qPCR). Pearson’s and Spearman’s correlation analyses were then performed to evaluate the relationship between Bacteroidetes and Firmicutes abundance, the clinical parameters, and plasma levels of the 2 miRs. Additionally, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was calculated to evaluate the potential of the 2 miRs as MetS biomarkers. Results: The 2 most abundant phyla were Bacteroidetes and Firmicutes. Bacteroidetes made up an average of 24.7% in the MetS group and 69.7% in the control group. Meanwhile, the average abundance of Firmicutes was 69.8% in the MetS group and 26.5% in the control group. The log F/B ratios in the MetS and control groups were 0.7 ± 0.5 and −0.4 ± 0.1 (p < 0.001), respectively. FDR analysis revealed significant correlations between Bacteroidetes abundance and BMI, DBP, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05), as well as between Firmicutes abundance and BMI, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05). Plasma levels of the 2 miRs differed significantly between the MetS and control groups: miR-122 (1.43 vs. 0.73; p = 0.0065) and miR-370 (1.39 vs. 0.83; p = 0.0089). The AUC values for miR-122 and miR-370 were 0.946 (p < 0.001) and 0.964 (p < 0.001), respectively. Pearson’s and Spearman’s correlation analyses revealed significant negative correlations between Bacteroidetes abundance and levels of miR-122 (p = 0.0048 and p = 0.0045, respectively) and miR-370 (p = 0.0003 and p < 0.0001, respectively), as well as significant positive correlations between Firmicutes abundance and levels of miR-122 (p = 0.0038 and p = 0.0027, respectively) and miR-370 (p = 0.0004 and p < 0.0001, respectively). However, as our exploratory findings were based on a small sample size, the high correlation results may partly reflect the separation between the MetS and control groups. Conclusions: Our exploratory findings suggest that the GM abundances of individuals with MetS may be significantly associated with plasma levels of miR-122 and miR-370, which are related to lipid metabolism. These miRs may therefore serve as potential MetS biomarkers. Full article

Osteoarthritis is a prevalent and disabling condition in companion dogs, yet existing treatments are primarily symptomatic and limited by safety concerns. EF-M2, a defined derivative of vitamin D-binding protein, selectively biases macrophages toward an anti-inflammatory phenotype in vitro. We conducted a randomised, double-blind, placebo-controlled trial (IMPAWS-OA-1) in 60 client-owned dogs with naturally occurring hip or elbow osteoarthritis. Animals were allocated to subcutaneous EF-M2 (0.1 µg/kg) given thrice weekly or twice weekly, or to saline placebo for four weeks, followed by four weeks off-drug. The primary endpoint was change in Canine Brief Pain Inventory–Pain Severity Score (CBPI-PSS) at Day 28. EF-M2 produced dose–frequency-dependent benefits: LS-mean ΔPSS was −2.11 for thrice weekly, −1.42 for twice weekly, and −0.54 for placebo (arm effect p < 0.001). Objective measures showed parallel improvements in peak vertical force and accelerometery. Serum biomarkers confirmed macrophage repolarisation (ARG1/iNOS ratio, IL-10 increase, TNF-α decrease), correlating with clinical response. Adverse events were infrequent and mild, with no excess over placebo. In conclusion, EF-M2 achieved clinically meaningful pain relief, functional gains, and biomarker shifts without safety signals, establishing first-in-species proof that targeted macrophage modulation may be a viable disease-modifying approach for canine osteoarthritis. Full article

This perspective provides a short overview of cancer biomarkers, balancing the technical details with the broad implications for biomarker discovery and innovation; early detection and screening; personalized treatment and monitoring; and emerging technologies. It also briefly discusses challenges in their clinical translation while exploring recent advancements and future implications for clinical practice. Finally, we offer thoughts on the role of artificial intelligence (AI) in biomarker development. AI is accelerating the discovery and validation of biomarkers by mining complex datasets, identifying hidden patterns, and improving the predictive accuracy. AI-powered tools enhance image-based diagnostics, automate genomic interpretation, and facilitate real-time monitoring of treatment responses. By integrating multi-omics data, AI offers new avenues for precision medicine and scalable cancer diagnostics, pushing biomarker development into a new era of intelligent, data-driven oncology. This editorial is a reflection on the state of biomarkers based on the contributions to the Special Issue “Cancer Biomarkers: Recent Progress, Innovations, and Future Clinical Implications”. Full article

Osteoarthritis (OA) is a multifactorial chronic musculoskeletal disorder characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Conventional diagnostic modalities, including radiographic imaging and symptom-based assessments, primarily detect disease in its later stages, limiting the potential for timely intervention. Inflammatory biomarkers, particularly Interleukin-6 (IL-6), Tumour Necrosis Factor-alpha (TNF-α), and Myeloperoxidase (MPO), have emerged as biologically relevant indicators of disease activity, with potential applications as companion diagnostics in precision medicine. This review examines the diagnostic and prognostic relevance of IL-6, TNF-α, and MPO in OA, focusing on their mechanistic roles in inflammation and joint degeneration, particularly through the activity of fibroblast-like synoviocytes (FLSs). The influence of sample type (serum, plasma, synovial fluid) and analytical performance, including enzyme-linked immunosorbent assay (ELISA), is discussed in the context of biomarker detectability. Advanced statistical and computational methodologies, including rank-based analysis of covariance (ANCOVA), discriminant function analysis (DFA), and Cox proportional hazards modelling, are explored for their capacity to validate biomarker associations, adjust for demographic variability, and stratify patient risk. Further, the utility of synthetic data generation, hierarchical clustering, and dimensionality reduction techniques (e.g., t-distributed stochastic neighbour embedding) in addressing inter-individual variability and enhancing model generalisability is also examined. Collectively, this synthesis supports the integration of biomarker profiling with advanced analytical modelling to improve early OA detection, enable patient-specific classification, and inform the development of targeted therapeutic strategies. Full article

Extracellular vesicles (EVs) are mediators of intercellular communication and serve as promising tools for drug discovery and targeted therapies. These lipid bilayer-bound nanovesicles facilitate the transfer of functional proteins, RNAs, lipids, and other biomolecules between cells, thereby influencing various physiological and pathological processes. This review outlines the molecular mechanisms governing EV biogenesis and cargo sorting, emphasizing the role of key regulatory proteins in modulating selective protein packaging. We explore the critical involvement of EVs in various disease microenvironments, including cancer progression, neurodegeneration, and immunological modulation. Their ability to cross biological barriers and deliver bioactive cargo makes them desirable candidates for precise drug delivery systems, especially in neurological and oncological disorders. Moreover, this review highlights advances in engineering EVs for the delivery of RNA therapeutics, CRISPR-Cas systems, and targeted small molecules. The utility of EVs as diagnostic tools in liquid biopsies and their integration into personalized medicine and companion diagnostics are also discussed. Patient-derived EVs offer dynamic insights into disease states and enable real-time treatment stratification. Despite their potential, challenges such as scalable isolation, cargo heterogeneity, and regulatory ambiguity remain significant hurdles. Recent studies have reported novel pharmacological approaches targeting EV biogenesis, secretion, and uptake pathways, with emerging regulators showing promise as drug targets for modulating EV cargo. Future directions include the standardization of EV analytics, scalable biomanufacturing, and the classification of EV-based therapeutics under evolving regulatory frameworks. This review emphasizes the multifaceted roles of EVs and their transformative potential as therapeutic platforms and biomarker reservoirs in next-generation precision medicine. Full article

Precision oncology, also known as personalized oncology or precision medicine, is the tailoring of cancer treatment to individual patients based on the specific genetic, molecular, and other unique characteristics of their tumor. The goal of precision oncology is to optimize the effectiveness of cancer treatment while minimizing toxicities and improving patient outcomes. Precision oncology recognizes that cancer is a highly heterogeneous disease and that each patient’s tumor has a distinct genetic diversity. Precision medicine individualizes therapy by using information from a patient’s tumor in the context of clinical history to determine optimal therapeutic approaches and increasing numbers of drugs target specific tumor alterations. Several targeted therapies with approved companion diagnostics are commercially available, the haves of precision oncology, where predictive biomarkers guide clinical decision-making and improve outcomes. However, many therapies still lack clear biomarkers, the have nots, posing a challenge to fully realizing the promise of precision oncology. Herein, we describe the current state of the art for breast cancer precision oncology and highlight the therapeutic agents that require a more robust biomarker. Full article

Chronic inflammatory enteropathies (CIEs) in companion animals represent a group of idiopathic, immune-mediated gastrointestinal disorders in which the intestinal epithelium can be altered, affecting intestinal functionality, nutrient absorption, and microbiota composition. This review presents an overview of markers that could be used for the assessment of intestinal health, focusing extensively on functional biomarkers, with particular attention to fatty acids (including short-chain fatty acids, SCFAs) and amino acids. Studies have consistently shown reduced concentrations of SCFAs in companion animals with CIEs compared to healthy groups. These alterations occur with varying intensity depending on the type of enteropathy. Alterations in saturated, monounsaturated, and long-chain polyunsaturated fatty acids have also been reported in blood and feces, particularly in omega-3 and omega-6 derivatives, as well as in the elongase and desaturase indices responsible for endogenous synthesis. In addition, amino acids serve as precursors to key metabolites involved in mucosal immunity, oxidative stress regulation, and microbial homeostasis. In CIEs, alterations in systemic and fecal amino acid profiles have been observed, reflecting both host metabolic adaptation and microbial dysbiosis. Integrating fatty acid and amino acid profiles can help distinguish different types of enteropathies, providing additional discriminatory power for determining response to dietary treatment. Future research should aim to elucidate the causal relationships between metabolic alterations and disease pathogenesis, which could lead to novel dietary interventions targeting metabolic interactions between the microbiota and the host. Full article

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, prevention, and treatment. Predictive biomarkers offer the potential to revolutionize clinical management, particularly in the preoperative setting, but their implementation requires careful consideration of ethical implications. This scoping review analyzes the ethical landscape of using immunohistochemistry (IHC) for molecular subtyping in PDAC, focusing on its utility, accessibility, and potential impact on patient care. We conducted a systematic literature search in the PubMed, Scopus and Google Scholar databases (2015–2025) using COVIDENCE, which identified 130 references. Of these, 79 were reviewed in a full-text format, and 9 ultimately met the inclusion criteria for our analysis. IHC offers several advantages as a companion diagnostic tool. It is relatively inexpensive, widely available in most pathology laboratories, and can be readily integrated into existing clinical workflows. This contrasts with more complex molecular subtyping methods, such as gene expression profiling, which can be costly, require specialized equipment and expertise, and may not be readily accessible in all clinical settings. Furthermore, accurate analysis of gene expression requires the localized targeting of individual cells; therefore, digesting the sample for bulk analysis would be less informative than using spatial localization techniques such as IHC. Because biomarker regulation can occur at the level of transcription or translation, protein-level assessment via IHC is often more accurate than mRNA analysis. Standardized IHC protocols for biomarker assessment are therefore essential for translating the molecular subtyping of PDAC into clinically actionable treatment strategies, especially for aggressive subtypes like basal-like tumors. This readily deployable IHC-based approach can optimize therapy selection, maximizing patient benefits and minimizing exposure to ineffective and potentially toxic treatments. This review critically analyzes the ethical dimensions of this method, grounded in the principles of autonomy, beneficence, non-maleficence, and justice. The review urges the medical community to fully utilize the potential of IHC-driven molecular subtyping to improve outcomes in PDAC, while ensuring equitable and responsible access to the benefits of precision oncology for all patients. Full article

The importance of lipid molecules present at the level of cell membranes is already well known. They can act as secondary messengers, participating in signal transduction processes that regulate various organ functions; furthermore, their nature significantly influences cellular properties and functions. Recent studies have seen how the lipid composition of cell membranes is connected to the animal lifespan and the onset of several pathological conditions. While numerous studies have been conducted aimed at characterizing the membrane lipidomic profile in the human field, in the animal field, especially in pets, the number of studies is very limited. In recent years, preliminary analyses have been conducted to provide initial information on the composition of membrane fatty acids in healthy pets and those with chronic enteropathy. The results of these studies are very interesting as they highlight differences in fatty acid composition between the two groups of animals. Obviously, a greater number of works is needed to obtain more reliable results and to analyze how the membrane lipid composition can vary in different breeds and sizes of dogs and cats in an attempt to understand the mechanisms underlying it. The present review is divided into three main parts: the first one examines the close influence of fatty acids on membrane properties/functions, the second one presents the main lipidomic analyses conducted so far on companion animals, and the third and final part summarizes the latest works on the link between membrane lipid profiles and animal lifespans, also focusing on dietary and non-dietary strategies able to influence it. Membrane lipidomics allows us to obtain a concrete overview of an animal’s metabolism and nutrition; furthermore, lipid alterations could be used as biomarkers for the early diagnosis of pathologies. This represents an innovative tool in the veterinary field to monitor the metabolic/health status of animals. Full article

This experiment aimed to assess the effects of both preweaning nutrition and postweaning growth rate on the resilience of dairy heifers from birth to 20 months of age. Immune competence and metabolic characteristics were assessed via repeated vaccine immune challenges throughout early life. Heifers were subject to either a high or low preweaning nutritional treatment (high: 8 L vs. low: 4 L of milk per day). Calves in these treatment groups were then equally divided into either a high or low postweaning growth rate treatment until 20 months of age. Nutritional intake, growth and metabolic data can be found in a companion paper, while the current paper outlines the responses to the three immune challenges. In the preweaning phase, heifers on a high milk volume had superior immune competence, demonstrated by higher monocyte and eosinophil counts. All other immune biomarkers were not different between treatments. By 8 months of age, the differences in monocytes were lost; however, the differences in preweaning eosinophil counts remained at 8 months and through to 13 months of age. At 13 months of age, there were also three-way interaction effects of preweaning nutrition, postweaning growth rate and vaccination for white blood cell count and neutrophil count; however, the trends in these responses appear random and do not align towards any clear advantages of pre- or postweaning nutrition. Metabolic responses to the immune challenges do not suggest any form of carryover effect from the preweaning phase and seemed to reflect the nutritional input at the time. Full article

Recent advancements in molecular biology have led to the discovery of potential biomarkers for the diagnosis of acute kidney disease (AKD) and chronic kidney disease (CKD). The use of multiple biomarkers in the diagnosis of kidney disease has the potential to enhance both specificity and sensitivity, enabling early detection and intervention that could ultimately reduce morbidity and mortality rates. This review provides an overview of studies on urine and blood biomarkers and examines their utility and significance in various clinical settings. Further and continuous research is needed to support the application of these biomarkers in clinical practice to facilitate early diagnosis, guidance for different interventions, and the monitoring of disease progression. Full article

Polymerase chain reaction (PCR) chips are advanced, microfluidic platforms that have revolutionized biomarker discovery and validation because of their high sensitivity, specificity, and throughput levels. These chips miniaturize traditional PCR processes for the speed and precision of nucleic acid biomarker detection relevant to advancing drug development. Biomarkers, which are useful in helping to explain disease mechanisms, patient stratification, and therapeutic monitoring, are hard to identify and validate due to the complexity of biological systems and the limitations of traditional techniques. The challenges to which PCR chips respond include high-throughput capabilities coupled with real-time quantitative analysis, enabling researchers to identify novel biomarkers with greater accuracy and reproducibility. More recent design improvements of PCR chips have further expanded their functionality to also include digital and multiplex PCR technologies. Digital PCR chips are ideal for quantifying rare biomarkers, which is essential in oncology and infectious disease research. In contrast, multiplex PCR chips enable simultaneous analysis of multiple targets, therefore simplifying biomarker validation. Furthermore, single-cell PCR chips have made it possible to detect biomarkers at unprecedented resolution, hence revealing heterogeneity within cell populations. PCR chips are transforming drug development, enabling target identification, patient stratification, and therapeutic efficacy assessment. They play a major role in the development of companion diagnostics and, therefore, pave the way for personalized medicine, ensuring that the right patient receives the right treatment. While this tremendously promising technology has exhibited many challenges regarding its scalability, integration with other omics technologies, and conformity with regulatory requirements, many still prevail. Future breakthroughs in chip manufacturing, the integration of artificial intelligence, and multi-omics applications will further expand PCR chip capabilities. PCR chips will not only be important for the acceleration of drug discovery and development but also in raising the bar in improving patient outcomes and, hence, global health care as these technologies continue to mature. Full article

Background: New safety concerns about targeted anticancer agents (TAAs) often emerge in the first few years after their initial regulatory approval. Our aim was to determine whether new serious and potentially fatal adverse drug reactions (ADRs) continue to emerge in the updated drug labels of TAAs several years after their initial regulatory approval and whether their emergence can be predicted. Methods: The updated drug labels of TAAs approved by the U.S. Food and Drug Administration before July 2013 were analyzed. Serious and potentially fatal ADRs were identified in the Warnings & Precautions (WPs) and Boxed Warnings (BWs) sections of the updated drug labels. Generalized linear mixed models were used to examine the associations between the number of adverse drug reactions and time, drug type (small molecules vs. monoclonal antibodies), and the availability of companion diagnostics for biomarkers. Results: Among 37 eligible TAAs, 25 (68%) were small molecules and 11 (30%) had available companion diagnostics for the biomarkers. Time was a significant predictor of new WPs (p ˂ 0.001) and BWs (p = 0.008). The updated drug labels of the small molecules received significantly more new WPs (p = 0.042) as compared to monoclonal antibodies. The availability of the companion diagnostics for the biomarkers did not have an impact on the emergence of new ADRs. Conclusions: New serious ADRs of TAAs continue to emerge in updated drug labels several years after their initial regulatory approval. Oncologists, regulators, and payers should be aware of the changing risk–benefit ratios of approved TAAs. Full article

Cancer is a leading cause of death among companion animals, with many cases diagnosed at advanced stages when clinical signs have appeared, and prognosis is poor. Emerging diagnostic technologies, including Artificial Intelligence (AI)-enhanced imaging, liquid biopsies, molecular diagnostics, and nematode-based screening, can improve early detection capabilities in veterinary medicine. These tools offer non-invasive or minimally invasive methods to facilitate earlier detection and treatment planning, addressing the limitations of traditional diagnostics, such as radiography and tissue biopsies. Recent advancements in comparative oncology, which leverage the biological similarities between human and companion animal cancers, underscore their translational value in improving outcomes across species. Technological advances in genomics, bioinformatics, and machine learning are driving a shift toward precision medicine, enabling earlier detection, personalized treatments, and monitoring of disease progression. Liquid biopsy testing detects circulating tumor DNA and tumor cells, providing actionable insights into tumor genetics without invasive procedures. Imaging systems enhance diagnostic precision, offering consistent and accurate tumor identification across veterinary practices, while portable innovations like Caenorhabditis elegans-based screening provide accessible options for underserved regions. As these technologies migrate from human medicine to veterinary applications, they are poised to redefine cancer care for companion animals. This review highlights key advancements in diagnostic technologies and their application in veterinary oncology, with a focus on enhancing early detection, accessibility, and precision in cancer care. By fostering the adoption of these innovations, veterinary oncology can achieve a new standard of care, improving outcomes for both animals and humans through the lens of comparative oncology. Full article

Postbiotics are emerging as potential functional ingredients for companion animal diets. This study aimed to determine if a Saccharomyces cerevisiae-based postbiotic can alter cytokine and stress responses to exercise and transport stress in adult Labrador Retrievers. Dogs received 15 g ground corn germ (Control, n = 12), 7.5 g postbiotic (Low, n = 12), or 15 g postbiotic (High, n = 12), daily for 63 days. Exercise was twice weekly for 7 weeks, and a single transport per dog occurred in week 8. Fecal inflammatory biomarkers, serum chemistries, and complete blood counts were assessed at the beginning and end of the study. Serum cytokines were quantified before and 18–20 h after the first and last exercise runs. Gait analysis was assessed before and 24 h after the first and final runs. Saliva cortisol was measured before and after transportation. Treatment did not affect blood chemistries, gait, fecal biomarkers, or saliva cortisol (p ≥ 0.19). Eosinophils increased slightly in Controls (p = 0.01), though remained below 0.80 × 10⁹ cells/L. Most cytokines were unaffected by treatment (p ≥ 0.15), but there were minor changes in circulating monocyte chemoattractant protein-1 (p = 0.01) and IL-8 over time at the initial run (p = 0.03) and IL-10 in males (p = 0.02) in the Low dose dogs. The High dose decreased Blautia (p = 0.04) slightly and tended to decrease Fusobacterium abundances (p = 0.07). The Low dose tended to increase Clostridium hiranonis (p = 0.07) slightly. The tested S. cerevisiae postbiotic produced small changes in immune function and gut microbial species in dogs. Full article