Search Results (323)

Background/Objectives: Severe bacterial sepsis and arboviral diseases may present with overlapping manifestations of vascular leakage, hemodynamic instability, thrombocytopenia, and organ dysfunction. We examined whether etiologically distinct severe infections may converge on selected components of immunovascular dysfunction and propose the Severe Infection-Mediated Vascular Activation and Collapse (SIMVAC) model as a hypothesis-generating framework. Methods: This narrative mechanistic review integrates human clinical and physiological studies, translational biomarker evidence, experimental models, and pathogen-specific mechanistic studies, with particular attention to the relative strength of evidence across arboviruses. Results: Dengue provides the strongest arboviral mechanistic support, linking plasma leakage with NS1-mediated endothelial barrier disruption, glycocalyx degradation, tissue-specific vascular effects, and inflammatory amplification. Evidence for yellow fever, West Nile virus, and Zika supports distinct organ-specific or systemic pathways but is less complete, whereas evidence for Mayaro, Oropouche, Venezuelan equine encephalitis, and Rocio viruses remains limited or hypothesis-generating. Candidate points of convergence include glycocalyx injury, Ang-2/Tie2 and S1P dysregulation, complement activation, NETosis, and vWF/ADAMTS13 imbalance. Conclusions: SIMVAC should be regarded as a testable conceptual model rather than a validated syndrome or diagnostic tool. Prospective, pathogen-confirmed studies are required to determine whether reproducible immunovascular signatures exist across severe infections and whether they provide clinically meaningful information beyond conventional etiological and severity assessment. Full article

Arthropod-borne viruses such as Alphaviruses and Flaviviruses are the causative agents of severe human disease, highlighted by fatal encephalitis and neurological sequelae in survivors. The lack of FDA-approved vaccines and therapeutics that can prevent or treat these infections results in a significant global disease burden. An important unmet need to address this capability gap is the need for affordable, scalable, clinically relevant human-based neuronal models to study neuroinvasive viruses and evaluate therapeutic options. Here, we described the application of a human neuronal precursor cell model, LUHMES (Lund human mesencephalic) cells, that can be differentiated into dopaminergic midbrain neurons and used to study virus infections. In this study, we demonstrated the susceptibility of LUHMES cells to infection by three arthropod-borne neurotropic viruses: Venezuelan equine encephalitis virus, dengue virus serotype 2, and West Nile virus. We also demonstrated how the model may be applied to evaluate potential therapeutic options using an FDA-approved small molecule, Omaveloxolone. Finally, we analyzed host cell responses to infection and treatment using gene expression and phospho-signaling analyses. These findings highlight the value of this model to interpret the pathogenic mechanisms of neurotropic viral infections and evaluate potential therapeutic intervention strategies in a clinically relevant in vitro human neuronal model. Full article

West Nile virus (WNV) transmission has intensified and expanded in Italy, but quantitative evidence on how local climatic and environmental conditions influence human risk in southern regions remains limited. This study examined the association between meteorological, environmental, and host-related factors and West Nile virus (WNV) cases at the municipal level in Apulia in 2023. Human WNV cases were georeferenced at the municipal level and linked to monthly indicators (minimum and maximum temperature, precipitation, surface water extent, green area coverage, land-use change, avian occurrence). A Bayesian spatio-temporal Poisson model with a conditional autoregressive structure was fitted to monthly counts of human WNV cases, with equine WNV cases, climatic, environmental and avian indicators included as covariates. Eight human WNV cases were reported between August and October and four equine WNV cases between September and November, with partial spatial and temporal overlap. In univariable analyses, the strongest associations were observed for meteorological variables, particularly temperature. In the final multivariable model, higher maximum temperature at a two-month lag was associated with increased WNV risk (RR = 1.53; 95% CrI: 1.18–2.23), while minimum temperature was excluded due to collinearity with maximum temperature. Green area coverage and water body extent showed uncertain effects. Model-based maps indicated that elevated fitted risk was concentrated in a narrow temporal window between August and October, expanding sharply across the region in September before receding, rather than describing a stable, spatially fixed hotspot. This exploratory analysis suggests that reported human WNV infections in Apulia in 2023 were temporally concentrated during the late summer/early autumn period and that maximum temperature at a two-month lag was positively associated with the outcome in the selected model. The findings are hypothesis-generating and should be interpreted with caution given the very small number of events, but they illustrate the feasibility of integrating multisource epidemiological, climatic, environmental, and veterinary data to support locally tailored early-warning efforts in southern Italy. Full article

Air quality in equestrian facilities is an important factor affecting equine respiratory health. This study evaluated particulate matter (PM), gaseous pollutants, and microclimatic parameters in a stable, an indoor riding arena, and an outdoor riding arena, and estimated the potential inhaled dust dose in horses under different exposure scenarios. Nine independent measurements were conducted at a height of 1.5 m in three locations. Concentrations of PM₁, PM_2.5, PM₁₀, respirable dust, total dust, and selected gaseous pollutants were measured. Four exposure scenarios combined 18 or 20 h spent in the stable with 4 or 6 h spent in the indoor or outdoor riding arena. Measurements were performed during summer under normal operating conditions at a university equestrian centre in Slovakia. The outdoor riding arena exhibited the highest concentrations of all PM fractions, whereas the indoor riding arena showed the lowest values (p < 0.05). Ammonia concentrations were higher in the stable than in the indoor riding arena, while the remaining gaseous pollutants showed only minor differences between facilities. Spatial mapping identified localized areas of elevated PM_2.5 and PM₁₀ concentrations, and exposure modelling demonstrated higher estimated inhaled mass of total and respirable dust for scenarios involving outdoor training. The results indicate that particulate matter, rather than gaseous pollutants, was the main factor affecting air quality. Reducing dust generation through appropriate riding surface management, regular maintenance, and air quality monitoring may help minimize inhalation exposure and improve the respiratory environment for horses. Full article

Synovitis is an inflammatory disorder in horses that contributes to cartilage degradation and osteoarthritis. This study evaluated the effects of intra-articular administration of high-molecular-weight (HMW), linear (non-cross-linked) hyaluronic acid (HA) in an equine model of lipopolysaccharide (LPS)-induced acute synovitis. In this randomized blinded study, acute synovitis was induced in radiocarpal joints of 16 adult horses using LPS (0.25 ng). After 12 h, joints were treated intra-articularly with either 2 mL of phosphate-buffered saline (PBS; control group) or 2 mL of HMW-HA (20 mg/mL; 2280 kDa; treatment group). Horses underwent orthopedic, ultrasonographic, and synovial fluid evaluations. Horses treated with HMW-HA exhibited lower synovial membrane thickening and reduced lameness scores compared with controls. Synovial fluid analysis demonstrated increased concentrations of HMW-HA during the acute inflammatory phase in treated joints. Reduced chondroitin sulfate release was also detected following HMW-HA administration. Lower lipid peroxidation levels (TBARS) were observed in the treated group at 24 h and 14 days. Intra-articular administration of high-molecular-weight linear hyaluronic acid was associated with increased synovial availability of HMW-HA during the acute inflammatory phase, attenuation of pain-related clinical signs and synovial membrane thickening, and modulation of the redox environment. These findings support a modulatory role of linear HMW-HA in the intra-articular environment. Full article

Joint inflammation and extracellular matrix degradation are major contributors to the development of equine osteoarthritis and reduced athletic performance. Alpha-2-macroglobulin is a naturally occurring broad-spectrum inhibitor of proteases and inflammatory mediators that has emerged as a promising orthobiologic therapy. This study investigated the anti-inflammatory and matrix-protective effects of alpha-2-macroglobulin-enriched plasma in complementary in vitro and ex vivo equine models. Primary equine chondrocytes and synoviocytes isolated from healthy horses were stimulated with interleukin-1β or lipopolysaccharide and treated with alpha-2-macroglobulin-enriched plasma or matched platelet-poor plasma. In parallel, an equine tendon explant model challenged with collagenase was used to evaluate extracellular matrix preservation. Alpha-2-macroglobulin-enriched plasma significantly reduced the production of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-13, downregulated interleukin-1β gene expression, and partially restored collagen type II expression in inflamed joint cells compared with platelet-poor plasma. In tendon explants, treatment preserved tissue architecture, reduced collagen degradation, and improved histological indices of matrix integrity under proteolytic challenge. These findings demonstrate that alpha-2-macroglobulin-enriched plasma exerts anti-inflammatory, anti-catabolic, and matrix-protective effects in experimental equine tissues. The results provide mechanistic support for the development of alpha-2-macroglobulin-based orthobiologic therapies as a complementary strategy for the management of synovitis and early osteoarthritis in horses. Full article

Background/Objectives: Vonoprazan is a potassium-competitive acid blocker with potential for the treatment of equine gastric ulcer syndrome. Vonoprazan metabolic pathways in horses have not been characterized. This study aimed to identify vonoprazan metabolites following oral administration and to determine the metabolic enzymes responsible for their metabolism using in vitro models. Methods: Six healthy adult Thoroughbred horses received vonoprazan (0.5 and 1 mg/kg PO) in a randomized crossover design. Plasma concentrations of vonoprazan-N-oxide (M-I) and vonoprazan-nitrone (M-III) were quantified using a validated liquid chromatography-tandem mass spectrometry method, and a non-compartmental pharmacokinetic analysis was performed. In vitro metabolism was evaluated using equine liver microsomes (ELMs) and equine recombinant CYP450 (eq-rCYP) enzymes. Enzyme kinetics were characterized using nonlinear regression modeling. Results: Both metabolites were detected in plasma after oral administration. Systemic exposure to M-I was markedly greater than M-III at both doses. At 1 mg/kg, mean ± SD C_max values were 39.2 ± 28.3 ng/mL for M-I and 1.67 ± 1.66 ng/mL for M-III. AUC_0–∞ increased dose-proportionally for both metabolites. In ELMs, M-I formation followed substrate inhibition kinetics, whereas M-III formation followed Michaelis–Menten kinetics. Among recombinant enzymes, CYP2D50 and CYP3A94 were the primary contributors to metabolite formation, exhibiting metabolite-specific kinetic profiles. Conclusions: These findings demonstrate that vonoprazan undergoes hepatic oxidative metabolism in horses, with M-I as the predominant circulating metabolite. Equine recombinants CYP2D50 and CYP3A94 appear to play central roles in equine vonoprazan metabolism, providing foundation for future evaluation of drug–drug interaction potential and clinical use in this species. Full article

Equine sarcoid is the most common cutaneous neoplasm of equids and represents a distinctive model of virus-associated tumor persistence. Although bovine papillomaviruses, particularly BPV-1 and BPV-2, are recognized as the main etiological agents, viral infection alone does not fully explain the clinical heterogeneity, frequent recurrence, and limited spontaneous regression of these lesions. This review summarizes current evidence on the molecular and cellular mechanisms underlying equine sarcoid pathogenesis, with emphasis on the interaction between BPV infection, host signaling pathways, tumor microenvironment dynamics, and multi-omic evidence of host regulatory networks. BPV oncoproteins, especially E5, promote fibroblast transformation through PDGFβR activation, downstream PI3K/AKT, MAPK and p38 signaling, altered cell survival, and immune evasion mediated by impaired antigen presentation. However, sarcoid persistence appears to depend on broader host-driven processes, including extracellular matrix remodeling, activated fibroblastic and myofibroblastic phenotypes, chronic inflammatory signaling, and ineffective immune clearance. Recent transcriptomic and epigenomic studies further indicate that long non-coding RNAs, DNA methylation changes, circulating microRNAs, and recently identified virus–host chimeric transcripts may contribute to stabilization of the neoplastic phenotype and may represent future biomarkers. Overall, this review proposes a virus-initiated, host-sustained conceptual framework for equine sarcoid pathogenesis, in which viral oncogene activity and host tissue reprogramming cooperate to promote lesion persistence, recurrence, and therapeutic resistance. Full article

This study aimed to investigate the effects of allogenic platelet-rich plasma (PRP) injection in lipopolysaccharide (LPS) inflamed equine radiocarpal joints. A preliminary study using a 0.0625 ng LPS dose was performed in the middle carpal joint and compared within animal to a saline control to confirm that synovitis was consistently produced using this dose. The main PRP effect study involved a bilateral 0.0625 ng LPS inflammation model with a within-animal comparison of LPS plus PRP versus a LPS plus saline control. Serial synovial fluid analysis was performed on samples obtained at post-injection hours (PIH) 0, 8, 24, 72, and 168. Synovial fluid analysis and clinical parameters were further complimented by objective gait and thermographic analyses. The 0.0625 ng dose induced a statistically significant increase in the synovial TP and WBC concentrations from baseline (p < 0.001) and control (p < 0.001, p = 0.013) values at PIH 8 in the preliminary study. No significant reduction in clinical or inflammatory markers was found in the PRP effect study, but a statistically significant increase in TP (p < 0.001) and PGE₂ (p < 0.001) from baseline and control at PIH 8 in the PRP group (p < 0.001) was identified, which returned to baseline by 72 and 24 h, respectively. The protocol used in this study generated PRP with a PDGF-BB concentration of 7889.76 pg/mL, TGF-ß1 concentration of 27,369.96 pg/mL and platelet count of 954 × 10⁹ cells/L. In conclusion, there does not appear to be any measurable anti-inflammatory effect of PRP treatment at this dose and treatment timing in this model of joint inflammation during the early inflammatory phase. Platelet-rich plasma appears to induce an increase in PGE2, although this increase was transient and self-limiting. Full article

Chronic synovial inflammation is a hallmark of osteoarthritis progression and is tightly regulated by synovial macrophages. Recently, voltage-gated sodium channels (NaV) have emerged as potent modulators of macrophage-driven inflammation, positioning them as novel therapeutic targets. Among selective NaV channel blockers, neosaxitoxin exerts remarkable anesthetic and immunomodulatory effects; however, its effects on joint inflammation upon intra-articular delivery remain unexplored. Using an equine model of bilateral carpal osteoarthritis, this study evaluated the immunomodulatory and tissue-preserving effects of intra-articular neosaxitoxin. Sixteen horses were randomized into two experimental groups (n = 8/each): Neosaxitoxin in one joint and triamcinolone (+control) in the contralateral joint; or neosaxitoxin in one joint and saline (−control) in the contralateral joint. Clinical parameters, synovial fluid cytology and cytokine profiles, and histological changes in synovium and cartilage were assessed over 30 days. Neosaxitoxin reduced synovial inflammation, evidenced by decreased synovial effusion and surface temperature, along with improved joint flexion. Furthermore, synovial fluid from neosaxitoxin-treated joints exhibited lower counts of erythrocytes, neutrophils, total protein, and key pro-inflammatory mediators (IL-1β and IL-6) compared to saline-treated controls. Histologically, neosaxitoxin-treated joints exhibited modest synovial inflammatory cell infiltration and minor cartilage abnormalities. In contrast, control joints exhibited synovial hyperplasia, fibrovascular proliferation, and cartilage degeneration. Our data suggests that intra-articular neosaxitoxin better preserved joint homeostasis by limiting synovial inflammation and cartilage damage. These results warrant further investigation on Neosaxitoxin as a candidate treatment for inflammatory arthropathies. Full article

Precision livestock farming (PLF) relies on high-precision three-dimensional (3D) horse reconstruction and automatic body measurement to support refined breeding management and health surveillance. However, data collection is restricted by building environment noise and hardware layout constraints; complex equine body shapes and large individual variations induce local geometric distortions in reconstructed models, limiting field deployment. Drawing on generative 3D reconstruction, this study develops the first image-to-3D pipeline that leverages three consumer depth cameras to reconstruct high-fidelity 3D horse models, integrating reconstruction, non-rigid optimisation and automatic body measurement. The image-to-3D module accurately extracts core morphological traits such as torso outlines and limb ratios for initial reconstruction. To eliminate local geometric deformation and recover scene scale, coarse-to-fine non-rigid fitting optimisation with dynamic surface feature matching weights is proposed, strengthening alignment between reconstructed meshes and real horse anatomical structures. Comparative experiments on multiple equine datasets verify that our method surpasses existing algorithms in measurement precision and reconstruction integrity. Compared with baseline methods, the non-rigid registration reduces core body measurement errors and Chamfer Distance (CD) by over 50%, while increasing the F-Score by more than 20%. This work enables automatic horse body phenotyping and offers technical references for image-to-3D dimensional measurement of other livestock species in large-scale precise breeding. Full article

This study investigated the interactive pathogenic characteristics of co-infection with Streptococcus equi (S. equi) and Streptococcus dysgalactiae (S. dysgalactiae) isolated from diseased foals. Integrating genomic analysis, in vitro phenotypic assays, and a murine intranasal infection model, we comparatively analyzed the biological traits and pathogenic differences between single and dual infections. Comparative genomic analysis revealed divergent virulence profiles between the two isolates, and both species harbored open pan-genomes. In vitro, the biofilm biomass of strain F1 was higher than that of all other groups. No synergistic hemolytic activity was observed in co-cultures of the two isolates. In vivo infection results indicated that streptococcal infection significantly altered the structure and abundance of pulmonary microbiota in mice. Furthermore, single and dual infections displayed strain-specific and time-dependent microbial disparities at early and late infection stages, which were associated with differential enrichment of multiple immune- and metabolism-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the Tumor Necrosis Factor (TNF) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways. Notably, co-infection triggered the most severe pulmonary microbiota dysbiosis and aberrant functional pathway regulation. This study preliminarily characterized the distinct phenotypic and pathological alterations induced by dual streptococcal infection, providing experimental evidence and novel insights for further exploring the interactive features of equine streptococcal mixed infections. Full article

Bioactive collagen peptides and collagen hydrolysates are dietary proteins whose degradation products also carry signaling activity. This second part of a two-part narrative review addresses the translational dimensions of their bioactivity, integrating veterinary clinical trials, controlled animal-model studies, and human biomedical data, with evidence strictly stratified by type. The gastrointestinal tract acts not only as the absorption site but as a target organ. In cell culture and rodent models, luminal collagen fragments restore tight-junction integrity, alter the microbiome, and shift the enterohepatic bile acid pool; increased secondary bile acid synthesis is proposed to engage the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). None of these steps have been demonstrated in veterinary clinical patients. The accompanying GLP-1 and PYY response may reflect direct amino acid stimulation of enteroendocrine cells as much as a bile acid-dependent route, and current data do not separate the two. Veterinary trials show objective kinetic improvement in osteoarthritic dogs and horses. Taurine-responsive dilated cardiomyopathy is a reversible, diet-amenable condition; as the principal bile acid conjugation substrate in carnivores, taurine acts on the same bile acid pool as a mechanistically separate input. Recent data implicate prolyl-hydroxyproline in brown adipogenesis, collagen peptides in hippocampal neurogenesis, and taurine in platelet normalisation. The gut–collagen peptide axis is an evolving model linking dietary collagen to systemic metabolic, endocrine, and immune signaling, with implications for companion-animal, equine, and livestock practice. Full article

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

Collagen, long regarded as the inert structural scaffold of the extracellular matrix, is now recognised as a source of bioactive signaling molecules: enzymatic hydrolysis releases low-molecular-weight bioactive collagen peptides that act systemically. This narrative review synthesises in vitro, animal-model, and veterinary clinical evidence with explicit differentiation of evidence levels; literature was identified through structured searches of PubMed, Web of Science, and Google Scholar, covering peer-reviewed, English-language reports published between 2000 and January 2026, without a formal systematic protocol. Across rodent, porcine, and human pharmacokinetic studies, orally administered collagen hydrolysate is efficiently absorbed, with a fraction reaching the circulation as intact prolyl-hydroxyproline and hydroxyprolyl-glycine through the conserved PEPT1/PEPT2 transporters; reported bioavailability varies with source, dose, and method, so no single value generalises across species. Native collagen and larger collagen fragments engage structure-dependent receptors in vitro (α2β1 integrins, DDR1/DDR2, GPVI, LAIR-1/2) that require triple-helical or Gly-Pro-Hyp presentation, whereas it is not established that the di- and tripeptides that reach the circulation after oral dosing engage them; their systemic actions are partly attributable to intracellular routes, including the Keap1–Nrf2 axis, HDAC/HAT modulation, and glycine-dependent glutathione synthesis. The gut–collagen peptide axis, a model derived from rodent and cell-culture data, links microbial bile acid remodeling and FXR/TGR5 signaling to systemic effects. Current evidence supports validated use in canine and equine osteoarthritis; species-specific bioavailability studies in dogs and cats remain the priority. Full article