Search Results (198)

Inflammatory diseases are common in companion dogs. Although white blood cell (WBC) count and C-reactive protein (CRP) are routinely used to assess systemic inflammation, their individual prognostic value remains limited. The erythrocyte sedimentation rate (ESR), reflecting red blood cell aggregation driven by plasma proteins, has long been applied in human medicine as both an inflammatory and prognostic marker. This study evaluated the prognostic utility of ESR in dogs, including clinically healthy and diseased populations. Associations between ESR, other inflammatory markers, and age were examined, and its role as an independent predictor of mortality and optimal clinical cut-off were determined. A subgroup of dogs meeting the systemic inflammatory response syndrome (SIRS) criteria were also analyzed to assess the latter’s usefulness in acute settings. A total of 350 dogs were enrolled: 241 diseased and 109 healthy. ESR was measured using an automated analyzer. Receiver operating characteristic (ROC) curve analysis, expressed as the area under the curve (AUC), evaluated diagnostic accuracy, followed by Kaplan–Meier survival and Cox proportional hazard analyses. ESR values were significantly higher in the disease group than in the healthy group (p < 0.0001). ESR showed fair to good prognostic accuracy for mortality in both the overall cohort (AUC = 0.776 [95% CI: 0.709–0.842]) and the SIRS subgroup (AUC = 0.846 [95% CI: 0.747–0.946]). An ESR cut-off of 18 mm/h was associated with mortality in SIRS dogs with 87.5% specificity. In the multivariate analysis, ESR showed an independent association with mortality (hazard ratio 1.013 [95% CI: 1.004–1.022], p = 0.004). These findings support ESR as a practical and independent prognostic marker for risk stratification in dogs with systemic inflammation. Full article

Postbiotics, which are preparations of inanimate microorganisms and their components, have emerged as a promising functional ingredient in animal health and nutrition. Postbiotics are primarily composed of microbial cell fractions, metabolites, enzymes, vitamins, polysaccharides, and short-chain fatty acids. Unlike probiotics, postbiotics do not contain live microorganisms, which strengthens their greater stability and safety in feed/food formulations. Postbiotics offer several beneficial effects, including antioxidant, anti-inflammatory, immune-modulatory, and antimicrobial actions. They enhance antioxidant enzymes, neutralize reactive oxygen species, and inhibit lipid peroxidation, thereby protecting tissues from oxidative damage. Postbiotics also inhibit pro-inflammatory molecules like TNF-α and IL-6, while enhancing the anti-inflammatory cytokine IL-10, promoting the maturation and function of immune cells, and increasing secretory IgA production. They suppress a variety of pathogenic bacteria, including Escherichia coli, Salmonella, Staphylococcus, Campylobacter, etc., both in vitro and in vivo. Moreover, they increase beneficial gut bacteria and improve the digestion and integrity of the intestine. This article outlines the beneficial effects of postbiotics in animals including poultry, swine, canine, feline, horses, and ruminant animals, either as feed/food or as a supplement. The integration of postbiotics into animal feed improves growth performance, feed conversion ratios, and disease resistance in animals. Thus, the multifunctional benefits of postbiotics make them a valuable tool for healthy companion animals and sustainable livestock production, supporting both animal welfare and productivity without the drawbacks associated with antibiotic growth promoters. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is a molecularly and pathogenically heterogenous disease with varying clinical outcomes, as reflected by the significant number of patients who develop relapse/refractory disease (rrDLBCL) following standard treatment with the combined R-CHOP regimen. The molecular background of rrDLBCL is not yet fully understood, and prognostic and/or companion diagnostic biomarkers for identification and treatment stratification of these patients are in high demand. Methods: This exploratory study used comprehensive proteomic data to identify proteins associated with treatment response. Proteome profiles of DLBCL cells were analyzed through groupwise comparison between cell lines with a resistant or sensitive response to rituximab, cyclophosphamide, doxorubicin, and vincristine. Their responses were determined using subsequent drug response screens, mimicking the conditions of diagnostic samples prior to treatment. Results: A total of 98 differentially abundant proteins, including NSFL1C, GET4, PCNA, and SMC5, were found between resistant and sensitive cells. These same 98 proteins were examined in two cohorts of DLBCL patients, leading to the identification of 16 proteins whose expression was consistently associated with treatment response both in vitro and in patient tissue samples. Among these, GET4 and NSFL1C showed the highest enrichment in R-CHOP resistant patients compared to sensitive responders. In the cell line study, GET4 was enriched in cyclophosphamide-resistant cell lines and NSFL1C enriched in vincristine-resistant cell lines, associating GET4 and NSFL1C enrichment in patient samples to responsiveness to cyclophosphamide and vincristine, respectively. Enrichment of DNA damage repair proteins was observed within the differential proteins, highlighting the need to investigate DNA damage repair involvement in treatment responses. Conclusions: This study identifies 16 proteins with concordant treatment response specificity in DLBCL cell lines and lymphoma tissue patient samples, suggesting their potential as prognostic markers for DLBCL. Full article

Cancer therapy is rapidly evolving from a one-size-fits-all paradigm toward highly personalized approaches. Traditional chemotherapies and radiotherapies, while broadly applied, often yield suboptimal outcomes due to tumor heterogeneity and are limited by significant toxicities. In contrast, precision oncology tailors prevention, diagnosis, and treatment to the individual patient’s genetic and molecular profile. Key advancements underscore this shift: molecularly targeted drugs (e.g., trastuzumab for HER2-positive breast cancer, EGFR and ALK inhibitors for lung cancer) have improved efficacy and reduced toxicity compared to conventional therapy. Pharmacokinetic (PK) and pharmacodynamic (PD) considerations are central to personalizing treatment, explaining variability in drug exposure and response among patients and guiding dose optimization. Modern strategies like therapeutic drug monitoring and model-informed precision dosing seek to maintain drug levels in the therapeutic range, improving outcomes. Immunotherapies, including checkpoint inhibitors and CAR-T cells, have transformed oncology, though patient selection via biomarkers (such as PD-L1 expression or tumor mutational burden) is critical to identify likely responders. Innovative drug delivery systems, notably nanomedicine, address PK challenges by enhancing tumor-specific drug accumulation and enabling novel therapeutics. Furthermore, rational combination regimens (informed by PK/PD and tumor biology) are being designed to achieve synergistic efficacy and overcome resistance. Key barriers include the high cost of biomarker testing, insufficient laboratory infrastructure, and inconsistent reimbursement policies. Operational inefficiencies such as long turnaround times or lack of clinician awareness further limit the use of precision diagnostics. Regulatory processes also remain complex, particularly around the co-development of targeted drugs and companion diagnostics, and the evidentiary requirements for rare subgroups. Addressing these barriers will require harmonized policies, investment in infrastructure, and educational initiatives to ensure that the promise of personalized medicine becomes accessible to all patients. Ensuring that advances are implemented responsibly—guided by pharmacological insights, supported by real-world evidence, and evaluated within ethical and economic frameworks—will be critical to realizing the full potential of personalized cancer medicine. Full article

Ovarian remnant syndrome (ORS) is a recognized postoperative complication in spayed dogs and cats, resulting from incomplete excision or inadvertent revascularisation of ovarian tissue during gonadectomy. Affected animals typically exhibit recurrent oestrous behaviour and may develop serious sequelae, including stump pyometra, mammary neoplasia, and granulosa cell tumours. This retrospective study evaluated 93 cases (70 dogs, 23 cats) diagnosed with ORS referred to the University Veterinary Hospital of Bologna, Italy, focusing on signalment, clinical presentation, diagnostic protocols, and treatment outcomes. Diagnosis relied on a multimodal approach combining clinical history, vaginal cytology, serum progesterone assays, ultrasonography, and histopathological examination of excised tissue. Surgical excision of residual ovarian tissue was the only curative treatment, with improved outcomes when performed during hormonally active phases of the oestrous cycle to optimize remnant localisation. Histopathology confirmed ovarian tissue in the majority of cases, with neoplastic transformation identified in 10% of dogs. Bilateral ovarian remnants were more prevalent than previously reported. Surgical revision was complicated by adhesions involving vital abdominal structures, emphasizing the need for meticulous technique. These findings highlight the critical importance of precise surgical technique during initial gonadectomy, early recognition of ORS, and comprehensive surgical management to prevent severe complications and promote companion animal welfare. Full article

Background/Objectives: Glypican-3 (GPC3) is a cell surface oncofetal protein that is highly expressed in hepatocellular carcinoma (HCC) but absent in normal liver tissue, making it an attractive target for molecularly targeted diagnosis and therapy. To support GPC3-targeted treatment strategies, there is a need for a non-invasive imaging tool capable of detecting GPC3-positive tumors. Methods: We conjugated a commercially available murine anti-GPC3 antibody (1G12), or a proprietary chimeric anti-GPC3 antibody (ET58) to the standard magnetic resonance imaging (MRI) contrast agent, gadolinium, via a DOTA chelator. The resulting probes, 1G12-DOTA-Gd or ET58-DOTA-Gd, respectively, were assessed for in vitro relaxivity and binding specificity to GPC3-positive HCC cells, as well as for in vivo imaging performance in mouse xenograft models bearing GPC3-positive or GPC3-negative HCC tumors. Conclusions: ET58-DOTA-Gd shows high specificity, imaging efficacy, and a favorable immunogenicity profile, thereby making it a promising candidate for clinical translation as a GPC3-targeted MRI probe. It holds potential as a non-invasive companion diagnostic for identifying GPC3-positive HCC patients who may benefit from GPC3-targeted therapies. Full article

Background/Objectives: Cervical Pap smears are routinely used to detect cellular abnormalities as a cervical cancer screening tool and to assess the presence of HPV for risk stratification of the disease. Here, we aimed to extend the applications of this sampling procedure by combining it with multicolor flow cytometry to characterize cell populations across cervical cancer disease stages. Methods: Cervical Pap smears from 30 patients with various disease stages ranging from normal to intraepithelial neoplasia up to treated cancers were analyzed as biofluids using multicolor flow cytometry. Individual samples were evaluated, and statistical analyses were performed over all sample stages. Cancer cell lines (CaSki, SiHa, HeLa, A549, U2OS) were examined as tumor cell controls. Results: Cervical biofluids were subdivided into cell populations according to their scattering properties and the expression of specific biomarkers: EpCAM and cytokeratin 8 for epithelial cells from tumors as well as healthy ectocervical and endocervical regions, and CD45 for immune cells. Discrimination of tumor cells was facilitated with cancer cell lines. Statistical analysis revealed that the composition of cell populations differs among disease stages, whereas treated cancer samples were consistently associated with a reduction in squamous epithelial cells and an increase in immune cells compared to normal samples. Conclusions: Herein, we identified the major cell populations in cervical biofluid samples and demonstrated that this method can detect changes in the cellular composition across different disease stages. This approach could be further exploited in cancer research and potentially serve as a companion diagnostic tool in tumor development, progression and during treatment. Full article

Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. “Trained immunity”—the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors—maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut–bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome–immune–neuronal axis interactions, and host genetic variants modulating microbiome–immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions. Full article

The use of the HOMA (Homeostatic Model Assessment) index in veterinary medicine is emerging as a promising and valuable method for evaluating insulin resistance and beta-cell function in companion animals, particularly in dogs and cats. Originally developed for use in human medicine, HOMA enables a minimally invasive assessment of glucose and insulin homeostasis, offering clinicians a practical tool for diagnosing and monitoring diabetes mellitus in animals. Its application in veterinary practice brings several advantages, including cost-effectiveness, ease of use, and the potential for early detection of metabolic disturbances before clinical symptoms appear. Nonetheless, important limitations persist, such as inter-individual variability, the effects of stress and comorbidities on glucose and insulin values, and the absence of standardized, species-specific reference ranges. These factors highlight the need for methodological refinement and the establishment of validated protocols tailored to the unique physiological characteristics of dogs and cats. Despite these challenges, HOMA represents a promising avenue for advancing the understanding of diabetes pathophysiology in veterinary patients. Future longitudinal studies and controlled trials are essential to confirm its reliability and enhance its clinical relevance. With further development, the HOMA index could become an essential tool in improving diagnostic accuracy and optimizing the management of diabetes in companion animal practice. 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

In vitro culture systems have advanced cancer biology, particularly through 2D and 3D tumor cultures. These have answered numerous scientific inquiries and propelled human oncologic research, with growing recognition of their potential to improve cancer treatment in companion animals, specifically cats and dogs. These species develop cancer spontaneously, closely resembling specific human cancer subtypes. For example, canine and feline mammary tumors are especially valuable for studying tumor biology. In vitro models from these tumors therefore offer a unique opportunity for veterinary cancer research. Recent 3D cell culture advancements provide promising platforms for predicting therapeutic responses in human cancer and may be applied to mammary tumors in animals. However, while limitations in fully recapitulating in vivo conditions and predicting chemotherapy response have been observed in colorectal tumoroids, similar challenges are emerging in mammary and breast tumors. In particular, canine mammary tumors and human breast cancers share critical heterogeneity and microenvironmental factors usually inadequately modeled in vitro. This review critically examines the predictivity of 3D mammary tumoroids from humans and companion animals, highlighting challenges related to stromal and immune cell preservation, reproducibility, and the translational gap between in vitro findings and clinical outcomes. We propose future directions to optimize these models for both comparative oncology and veterinary-specific applications. Full article

Background/Objectives: Diabetes mellitus (DM) is an increasingly prevalent endocrine disorder affecting humans and companion animals. Type 1 DM (T1DM) and type 2 DM (T2DM) are well characterized in humans, and canine DM most often resembles T1DM, marked by insulin dependence and β-cell destruction. Conversely, feline DM shares key features with human T2DM, including insulin resistance, obesity-related inflammation, and islet amyloidosis. This review provides a comprehensive comparative analysis of antidiabetic therapies in humans, dogs, and cats, focusing on three core areas: disease pathophysiology, pharmacological and delivery strategies, and translational implications. In human medicine, a wide array of insulin analogs, oral hypoglycemic agents, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists (liraglutide) and sodium-glucose cotransporter-2 inhibitors (empagliflozin), are available. Veterinary treatments remain limited to species-adapted insulin formulations and off-label use of human drugs. Interspecies differences in gastrointestinal physiology, drug metabolism, and behavioral compliance influence therapeutic efficacy and pharmacokinetics. Recent innovations, such as microneedle patches for insulin delivery and continuous glucose monitoring systems, show promise in humans and animals. Companion animals with naturally occurring diabetes serve as valuable models for preclinical testing of novel delivery platforms and long-acting formulations under real-world settings. While these technologies show potential, challenges remain in regulatory approval and behavioral adaptation in animals. Conclusions: Future research should prioritize pharmacokinetic bridging studies, veterinary-specific formulation trials, and device validation in animal models. By highlighting shared and species-specific characteristics of DM pathogenesis and treatment, this review advocates a One Health approach toward optimized antidiabetic therapies that benefit human and veterinary medicine. Full article

The transition from a normal to a cancerous cell involves a multistep process driven by genetic alterations. Malignant cells progressively acquire traits that enhance their survival within the host, including the ability to evade apoptosis, stimulate neovascularization, and escape immune surveillance. These adaptations allow cancer to grow uncontrollably, invade adjacent tissues, and metastasize to distant organs, ultimately impairing normal physiological functions and complicating treatment efforts. Among the most significant clinical challenges is chemotherapy resistance, which diminishes the effectiveness of conventional therapies and contributes to disease progression. Addressing this issue requires integrated and multidisciplinary approaches. This review investigates and compares the mechanisms of chemotherapy resistance identified in humans and companion animals. By examining both shared and species-specific features, this analysis aims to support the development of more effective and translational treatment strategies. Full article

The cross-species spillover of coronaviruses is considered a serious public health risk. Feline coronavirus (FCoV), canine coronavirus (CCoV), and transmissible gastroenteritis virus (TGEV) are all classified under Alphacoronavirus suis and infect companion animals and livestock. Due to their frequent contact with humans, these viruses pose a potential risk of future cross-species transmission. Molnupiravir, a prodrug of N4-hydroxycytidine, exhibits potent antiviral activity against SARS-CoV-2, a member of the Betacoronavirus genus, and has been approved for the treatment of COVID-19. Molnupiravir was recently shown to be effective against FCoV, suggesting broad-spectrum antiviral activity across coronavirus lineages. Based on these findings, the present study investigated whether molnupiravir is also effective against CCoV and TGEV, which belong to the same Alphacoronavirus suis species as FCoV. We examined the in vitro antiviral effects of molnupiravir using four viral strains: FCoV-1 and -2, CCoV-2, and TGEV. Molnupiravir inhibited plaque formation, viral antigen expression, the production of infectious viral particles, and viral RNA replication in a dose-dependent manner in all strains. IC₅₀ values for CCoV-2 and TGEV, calculated using a feline-derived cell line (fcwf-4), were significantly lower than those for FCoV, suggesting higher sensitivity to molnupiravir. These results demonstrate that molnupiravir exhibited broad antiviral activity against animal coronaviruses classified under Alphacoronavirus suis, providing a foundation for antiviral strategies to mitigate the future risk of cross-species transmission. Full article

The development of interoperable and reusable information models is a key challenge for digitalization in manufacturing domains with heterogeneous and complex process chains. Ensuring seamless data exchange requires the standardization of both data syntax and semantics, while maintaining compatibility with existing industry standards. This paper presents a methodology for deriving standardizable and generalizable OPC UA information models tailored to domains with high process variability and interdisciplinary requirements. The methodology integrates system analysis, parameter mapping, and the development of modular submodels, supported by expert input and validation. It emphasizes the reuse and extension of existing OPC UA Companion Specifications to reduce complexity, avoid redundancy, and enable long-term standardization. The approach is exemplified by its application to battery cell production, an emerging manufacturing domain combining process and mechanical engineering with continuous and discrete processes. Its high degree of heterogeneity and lack of domain-specific standards pose significant challenges for model development. Through iterative expert workshops and structured model validation, a dedicated and transferable OPC UA framework is created. The resulting layered model structure combines a cross-industry standard with newly developed, process-aware model elements. This enables both broad applicability and the depth required for complex production environments, while supporting use cases such as traceability, regulatory reporting (e.g., EU Battery Passport), and process optimization. The resulting model improves interoperability, transparency, and data integration, offering a scalable blueprint for other complex manufacturing sectors. Full article