Journal of Veterinary Science最新文献

Importance: Cerebral ischemia arises from insufficient blood flow to the brain, resulting in substantial metabolic disturbances. Baicalin, a flavonoid compound derived from Scutellaria baicalensis, has anti-inflammatory, antioxidant, and neuroprotective properties.

Objective: To identify proteins regulated by baicalin in a rat model of ischemic stroke.

Methods: Adult male Sprague Dawley rats underwent middle cerebral artery occlusion (MCAO) or sham surgery and received intraperitoneal baicalin (100 mg/kg) or vehicle 1 h before surgery. Neurobehavioral assessments were performed 24 h after MCAO, and cerebral cortex tissues were collected. Cortical damage was evaluated using 2,3,5-triphenyltetrazolium chloride staining and hematoxylin-eosin staining. Protein expression changes between groups were assessed by liquid chromatography-tandem mass spectrometry, and selected targets were validated by reverse transcription-polymerase chain reaction.

Results: MCAO induced marked neurological deficits, infarction, and histopathological damage, all of which were significantly attenuated by baicalin treatment. MCAO decreased adenylate cyclase type 1 and solute carrier family 25 member 12 levels, and baicalin mitigated these reductions. Baicalin also reduced MCAO-induced increases in C-reactive protein and apolipoprotein C-II, as well as alpha-1 microglobulin, murinoglobulin, and hemoglobin subunit B, proteins associated with inflammation, lipid metabolism, mitochondrial function, and cellular injury.

Conclusions and relevance: Baicalin exerts neuroprotective effects in cerebral ischemia by modulating proteins involved in energy metabolism, myelination, and neuroinflammation. These findings support baicalin as a promising therapeutic candidate in experimental stroke models.

In October 2024, the Asian Association of Veterinary Schools hosted "VetEd Asia 2024," a symposium to promote veterinary education and collaborations in Asia, held in Daejeon, Republic of Korea. The event was co-organized with the Federation of Asian Veterinary Associations and the American Association of Veterinary Medical Colleges' Council on International Veterinary Medical Education and with the support of the World Organisation for Animal Health Regional Representation for Asia and the Pacific. The symposium brought together diverse stakeholders in veterinary education, facilitated networking, and highlighted emergent topics such as education research aimed at improving the quality of education in the region. These collaborative efforts are expected to strengthen veterinary education standards and outcomes, resulting in the development of a stronger veterinary workforce.

Importance: Canine heartworm disease remains a major global health issue. Despite the wide availability of ivermectin (IVM) formulations, pharmacokinetic and bioequivalence data are limited.

Objective: This study evaluated the pharmacokinetics and bioequivalence of eight oral IVM formulations (B-I) compared with the innovator product (A) in dogs.

Methods: Forty-five healthy dogs (mean body weight: 14.3 kg) were divided into nine groups (n = 5). Each received 6.2 µg/kg of IVM orally. Blood samples were collected up to 72 h post-dosing, and plasma IVM concentrations were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were analyzed using a one-compartment model. Bioequivalence was assessed non-compartmentally using 90% confidence intervals for maximum concentration (C_max) and area under the plasma concentration-time curve (AUC_72h), with acceptance limits of 80-125%.

Results: Absorption (Ka = 0.09-0.16 h⁻¹), elimination half-life (T1/2 = 4.89-14.97 h), and systemic exposure (C_max = 6.07-7.59 ng/mL) varied among formulations. Formulation C showed prolonged elimination (14.97 h) and higher exposure (AUC_72h = 214.16 ng·h/mL), whereas formulation H exhibited faster absorption but lower exposure (AUC_72h = 114.36 ng·h/mL). Simulated dosing indicated that most formulations maintained plasma levels above the minimum effective concentration (0.2 ng/mL), except formulation E. Only formulation G met full bioequivalence with the reference product.

Conclusions and relevance: All formulations achieved plasma concentrations sufficient for prophylaxis, but only B, C, and G satisfied bioequivalence criteria. Larger sample sizes and standardized evaluation guidelines are recommended for multi-formulation bioequivalence studies.

Importance: The programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway transmits negative immunoregulatory signals. Blocking this pathway using peptides or antibodies can restore immunity.

Objective: To evaluate the immune function of epitope peptides interacting with porcine PD-1 or PD-L1.

Methods: We optimized and synthesized peptides (PD-L14QN-GF and PD-L14QN-AF) using the solid-phase method and assessed their effects on peripheral blood mononuclear cell (PBMC) proliferation and PD-1 and cytokine expression after porcine reproductive and respiratory syndrome virus (PRRSV) infection in vitro and on antibody responses to a porcine circovirus type 2 (PCV2) vaccine in vivo.

Results: The optimized peptides PD-L14QN-GF and PD-L14QN-AF exhibited lower binding free energy and higher stability when interacting with the PD-1 target protein. Under both PRRSV-infected and non-infected conditions in vitro, both peptides enhanced the proliferation of PBMCs, inhibited PRRSV RNA replication, and downregulated PD-1 transcription levels. Additionally, PD-L14QN-GF and PD-L14QN-AF upregulated the mRNA transcription and protein secretion of interleukin (IL)-2, IL-10, and interferon-γ to varying degrees. In vivo experiments demonstrated that PD-L14QN-GF significantly increased the antibody titer and seroconversion rate of the PCV2 vaccine.

Conclusions and relevance: PD-L14QN-GF and PD-L14QN-AF induced stronger immune responses than PD-L14. PD-L14QN-GF has potential as an immune-enhancing adjuvant.

Importance: Kluyvera intermedia (K. intermedia) is an emerging pathogen associated with respiratory disease in pigs. Its multidrug resistance poses a significant threat to livestock health.

Objective: This study characterized the resistance phenotype and genotype of K. intermedia L-40-1, isolated from a pig in Jilin Province, China, and investigated the genomic determinants of its antibiotic resistance.

Methods: 16S rRNA sequencing was performed to identify the strain. The resistance phenotype was assessed by determining minimum inhibitory concentrations (MICs), and resistance determinants were characterized by whole-genome sequencing. Comparative genomic analysis against the national center for biotechnology information (NCBI) database of K. intermedia strains was conducted to determine phylogenetic relationships and resistance gene profiles.

Results: L-40-1 exhibited high resistance to β-lactams, cephalosporins, macrolides, aminoglycosides, and sulfonamides. Comparative analysis identified 19 high-frequency resistance genes (e.g., arnT, rsmA, emrR, and acrA). A 159,618 bp plasmid (PYL-8) harbored multiple resistance genes (e.g., sul1, dfrA27, qnrB6, and tet(D)) and transposons (e.g., IS6, IS1, and Tn3), contributing to its multidrug resistance. Chromosomal and plasmid-borne resistance mechanisms were identified.

Conclusions and relevance: K. intermedia L-40-1 uses a combination of chromosomal and plasmid-mediated resistance genes, facilitated by transposons, to confer multidrug resistance. This highlights the need for surveillance of K. intermedia in livestock to mitigate the spread of antibiotic resistance.

Importance: Cryptorchidism, defined as the failure of one or both testes to descend into the scrotum, is a pathological condition that adversely impacts testicular development and spermatogenic function. In livestock, particularly bulls, such impairment can lead to substantial economic losses due to compromised fertility. A comprehensive understanding of the morphological and molecular alterations associated with cryptorchidism is essential for efforts to develop effective diagnostic and therapeutic strategies.

Objective: This study aimed to examine morphological changes and changes in the extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB) activity in the testes of bulls with cryptorchidism.

Methods: Testes from the 18-month-old unilateral cryptorchid bulls, including the descended (normal) and undescended (cryptorchid) testes from each animal, were analyzed through gross examination, histology, immunohistochemistry (Ki-67, phosphorylated p-ERK, p-CREB), and Western blotting.

Results: Cryptorchid testes were smaller and exhibited reduced epithelial thickness, although seminiferous tubule area remained unchanged. Expression of Ki-67, p-ERK, and p-CREB was significantly decreased, indicating impaired cell proliferation and signaling. Total ERK and CREB protein levels were unchanged, but phosphorylation levels were notably reduced in cryptorchid samples.

Conclusions and relevance: Our findings demonstrate that cryptorchidism alters testicular morphology and disrupts key signaling pathways, particularly those involved in cell growth and function. Such alterations may contribute to infertility and highlight the importance of early diagnosis and intervention in the context of reproductive management in livestock.

Importance: Mesenchymal stem cells (MSCs) play a pivotal role in advancing veterinary regenerative medicine in dogs and cats and serve as valuable preclinical models for human therapies. Despite their widespread application, fundamental knowledge gaps and the absence of standardized criteria for canine and feline MSCs remain. This review focuses exclusively on direct comparative studies across species and tissue sources to support evidence-based practices in which clinical use often precedes full scientific validation.

Observations: This review consolidates available comparative studies of canine and feline MSCs, categorizing them by species, tissue origin, and donor factors. We systematically assessed fundamental biological properties of MSCs (yield, morphology, proliferation, differentiation) and functionalities (immunomodulation, angiogenesis, migration). Overall, MSCs from both species exhibit properties comparable to those of human MSCs. However, canine MSCs have been more extensively studied across diverse tissues, whereas feline MSC research remains primarily restricted to adipose tissue and bone marrow. Notable interspecies and tissue-specific differences include proliferation rate, chondrogenic potential, and surface marker variability. Donor factors such as age also influence MSC behavior. Nevertheless, inconsistencies in sampling sites, culture protocols, and surface marker panels across studies continue to pose challenges for achieving a comprehensive understanding through direct comparison.

Conclusions and relevance: Establishing consistent characteristics of MSCs in companion animals requires well-designed and controlled comparative studies. Standardization of MSC characterization, production, and application has been widely advocated. This review highlights ongoing efforts to address species- and tissue-specific knowledge gaps and emphasizes the need for additional comparative research to strengthen the preclinical and therapeutic utility of MSCs, thereby advancing evidence-based stem cell therapies in veterinary medicine.

Importance: The raccoon dog (Nyctereutes procyonoides), native to East Asia, is a key reservoir of zoonotic diseases, crucial for understanding tick-borne pathogen (TBP) transmission in ecosystems.

Objective: This study aimed to assess the prevalence of Rickettsiales pathogens including Anaplasma, Ehrlichia, and Rickettsia species in raccoon dogs across South Korea over a three-year period (2021-2023).

Methods: A total of 275 blood samples were collected from raccoon dogs across nine wildlife centers in South Korea. Molecular detection of pathogens was conducted using polymerase chain reaction to identify Anaplasma, Ehrlichia, and Rickettsia species.

Results: The study revealed an overall infection rate of 10.5% for Anaplasma phagocytophilum and 0.4% for Rickettsia conorii ssp. raoultii. Notably, this represents the first molecular detection of R. conorii ssp. raoultii in raccoon dogs. No samples tested positive for Ehrlichia spp. The central region of South Korea geographically had the highest prevalence of A. phagocytophilum, while all cases of R. conorii ssp. raoultii were detected in the northern region.

Conclusions and relevance: These findings highlight the raccoon dog as a reservoir for TBPs, especially A. phagocytophilum and R. conorii ssp. raoultii, and emphasize the need for further research on its role in public health and zoonotic disease ecology in South Korea.

Importance: Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus that threatens the pig industry and acts as a viral spillover, infecting other farm animals and potentially humans. The recent emergence of highly pathogenic PDCoV in South Korea, causing severe neonatal piglet mortality, underscores the urgent need for effective countermeasures to mitigate economic and public health risks. Thus, discovering new therapeutic methods through drug repurposing is crucial for controlling PDCoV.

Objective: This study investigated ivermectin (IVM) for its antiviral effect on PDCoV in vitro and explored its mechanism of action.

Methods: The antiviral effects and mechanism of action of IVM against PDCoV were evaluated using various virological assays.

Results: IVM markedly impaired the replication of PDCoV in a dose-dependent manner. Time-of-addition assays showed that the anti-PDCoV activity of IVM was most potent when administered before infection, simultaneously with infection, or immediately after infection. Further mode of action experiments revealed that IVM targeted the replication stage of PDCoV infection at post-entry steps.

Conclusions and relevance: Our results indicated that IVM interfered with PDCoV genome replication by impairing viral RNA synthesis. These findings suggest the potential of IVM for inhibiting PDCoV RNA polymerase and provide an invaluable therapeutic strategy to combat PDCoV infection with IVM, offering a viable alternative in the absence of commercial vaccines.

Importance: Leishmaniasis, caused by Leishmania parasites, is a significant global health issue with limited treatment options. Mitogen-activated protein kinase 3 (MAPK3) plays a crucial role in parasite survival and immune evasion, making it a promising therapeutic target. Nevertheless, existing treatments have substantial side effects, and no specific MAPK3 inhibitors are available.

Objective: This study evaluated the potential MAPK3 inhibitors capable of targeting L. donovani and L. martiniquensis using computational and experimental approaches.

Methods: Five compounds from the NCI database were screened using an ADP-Glo Kinase Assay for MAPK3 inhibition. Half-maximal inhibitory concentration (IC₅₀) analysis was performed to determine their potency. Molecular docking and molecular dynamics simulations were conducted to assess the binding interactions and stability. Cell-based assays were performed to evaluate the efficacy of these compounds against L. donovani and L. martiniquensis in the promastigote and amastigote stages.

Results: NSC107522, NSC196515, and NSC84100 inhibited MAPK3, with IC₅₀ values of 2.69 µM, 4.96 µM, and 10.59 µM, respectively. NSC107522 showed the strongest binding affinity (ΔG_bind = -111.20 kJ/mol) and reduced L. donovani survival in the promastigote (IC₅₀ = 2.68 µM) and amastigote (IC₅₀ = 4.04 µM) stages. NSC84100 exhibited superior activity against L. martiniquensis, with IC₅₀ values of 3.14 µM (promastigotes) and 2.61 µM (amastigotes).

Conclusions and relevance: NSC107522 and NSC84100 are promising MAPK3 inhibitors with species-specific activity. NSC107522 targets L. donovani, while NSC84100 is more effective against L. martiniquensis. These findings provide a foundation for developing targeted therapies against leishmaniasis, but further studies will be needed to determine their in vivo efficacy and optimize MAPK3-targeted drug design.