{"title":"A multi-target mRNA Vaccine Provides Cross-Prophylactic and Therapeutic Protection Against Diverse Pasteurellaceae Infections","authors":"","doi":"10.29261/pakvetj/2026.162","DOIUrl":"https://doi.org/10.29261/pakvetj/2026.162","url":null,"abstract":"Pasteurellaceae pathogens, including P. multocida, pose significant threats to humans, livestock, and poultry, while the effectiveness of antibiotic treatment is gradually being compromised by the problem of antibiotic resistance.Here, we developed a conserved multi-target mRNA vaccine strategy to achieve broadspectrum prevention and therapy against Pasteurellaceae infections.Six highly conserved intracellular antigens, with truncated sequence similarities all exceeding 91%, were selected for the development of a novel mRNA platform against Pasteurellaceae.In mouse models, the vaccine conferred strong protection against P. multocida and showed cross-protection against four Pasteurellaceae pathogens, reducing lung bacterial burden by up to 10-fold compared with the challenge control.In a rabbit acute pneumonia model, the vaccine significantly improved survival by over 40% and reduced lung pathology following P. multocida infection.Notably, repeated administration of vaccine exhibited preliminary therapeutic efficacy in naturally infected animals, including one cat, piglets (with a 40% reduction in infection rate), and laying hens (with an approximately 20% increase in egg production), resulting in bacterial burden and alleviation of clinical symptoms.These findings demonstrate that a conserved multi-antigen mRNA vaccine can induce broad-spectrum protective effect against Pasteurellaceae pathogens.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2026.162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Selenium Nanoparticles Synergistically with Curcumin to Attenuate Diquat-Induced Broiler Intestinal Oxidative Stress Via NF-κB & Apoptotic Pathways","authors":"","doi":"10.29261/pakvetj/2026.174","DOIUrl":"https://doi.org/10.29261/pakvetj/2026.174","url":null,"abstract":"In poultry production, nutrient digestion and absorption in the intestine generate reactive oxygen species (ROS), which disrupt antioxidant balance in the intestinal mucosa and trigger oxidative stress.Diquat, a bipyridyl herbicide, exacerbates intestinal oxidative injury by inducing excessive ROS production.Both selenium nanoparticles (SeNPs) and curcumin are widely used feed additives with proven antioxidant and growth-promoting properties that target inflammation and apoptosis pathways.Their combined use may yield stronger synergistic protection against oxidative damage and help maintain intestinal barrier integrity.The present research investigated the protective efficacy of co-supplementing SeNPs and curcumin against diquat-induced oxidative stress in broilers, specifically focusing on their impact on redox balance, gut barrier integrity, and underlying signaling pathways.Results showed that, compared with the diquat-only group (apoptosis rate: 93.12%±0.04),co-supplementation of SeNPs (1.0mg/kg) with curcumin (150 or 300mg/kg) markedly reduced jejunal cell apoptosis (48.03%±0.06 and 38.06%±0.05,respectively; P<0.01), with greater efficacy than either compound alone.RT-qPCR analysis revealed that the combination significantly suppressed mRNA expression of key genes in the apoptotic and NF-κB pathways at 24h and 7 days post-diquat challenge.Collectively, SeNPs and curcumin act synergistically to mitigate diquat-induced oxidative stress and enhance jejunal antioxidant capacity in broilers primarily by inhibiting apoptosis and NF-κB signaling.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2026.174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prunella vulgaris L. Polysaccharide Alleviated Liver Injury in Carbon Tetrachloride-Induced Mice Via Regulating Oxidation Resistance, Inflammatory Response and Microbiota","authors":"","doi":"10.29261/pakvetj/2026.025","DOIUrl":"https://doi.org/10.29261/pakvetj/2026.025","url":null,"abstract":"Prunella vulgaris L. (P.vulgaris L.) is a traditional medicinal herb renowned for its various pharmacological properties through antioxidant and anti-inflammatory effects.The present study investigated the hepatoprotection of P. vulgaris L. polysaccharide against carbon tetrachloride-induced liver injury in mice.Thirty (n= 30) ICR mice were divided into a control group (AC), a CCl4-induced liver injury model (AM), and a P. vulgaris L. polysaccharide treatment group (AXK).The AM and AXK groups received intraperitoneal injections of 10% CCl4 every two days, while the AXK group was also intragastrically administered P. vulgaris L. polysaccharide @150 mg/kg/day.The present research indicated that CCl4 remarkably decreased liver weight (P<0.05) and liver index (P<0.001) in mice, while treatment with P. vulgaris L. reversed these changes.Histopathological observation indicated that structural injury of the liver and the infiltration of inflammatory cells were alleviated, and Sirius Red-positive collagen deposition was qualitatively reduced in the AXK group compared to the CCl4 model group.Moreover, P. vulgaris L. significantly decreased liver function markers such as ALT and AST (P<0.001),inflammation factors like IL-6 (P<0.01),IL-1 (P<0.01),TNF- (P<0.05), and oxidative stress marker MDA (P<0.01), while increasing GSH-Px (P<0.001),T-AOC (P<0.01),SOD (P<0.01) and IL-10 (P<0.01)levels.Analysis of gut microbiota suggested that P. vulgaris L. improved intestinal flora by reducing harmful bacteria such as Colidextribacter and Mammaliicoccus, while increasing Lachnospiraceae UCG-006, Coriobacteriales Incertae Sedis, and Streptomyces.This study provides a complete profile of the influence of Prunella vulgaris L. on the morphology of the liver, inflammation factors, oxidative stress parameters, and intestinal microbiota in CCl4-challenged mice and suggests that Prunella vulgaris L. polysaccharides may exert hepatoprotection in relation to favorable modulation of the gut-liver axis.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2026.025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147878884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"C6 Ceramide Induces Apoptosis of Canine Oral Melanoma by Attenuating the Wnt/β-catenin Signaling","authors":"","doi":"10.29261/pakvetj/2025.320","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.320","url":null,"abstract":"Melanoma is prevalent in canine oral tumors.C6 ceramide exerts powerful antitumor activity in multiple types of cancer in various ways.In this study, we investigated the functions of C6 ceramide in canine melanoma cells and xenograft models and elucidated its mechanism.The results showed that C6 ceramide significantly inhibits canine oral melanoma cell growth, migration, and invasion, as well as in xenograft models.Moreover, significant alterations were observed in cell cycle distribution and apoptosis.Subsequently, upregulations of caspase 8 and 3 were found, indicating that C6 ceramide activated the extrinsic apoptotic pathway.Finally, the expressions of p-GSK3Ser9 and -Catenin were significantly reduced following C6 ceramide treatment, while no changes were observed in GSK3.In conclusion, C6 ceramide exhibits remarkable antitumor activity by triggering the extrinsic apoptotic pathway and inactivating Wnt/-catenin signaling in canine oral melanoma.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147917576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Glutamate Dehydrogenase 1 in Congenital Obstructive Nephropathy: Insights from Neonatal Rodent Models and Implications for Veterinary Medicine","authors":"","doi":"10.29261/pakvetj/2025.341","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.341","url":null,"abstract":"Congenital obstructive nephropathy (CON) refers to kidney damage caused by impaired urine flow due to congenital malformations of the urinary tract.CON is a leading cause of chronic kidney disease (CKD) in young animals, particularly in dogs and cattle, characterized by congenital urinary tract obstruction-induced renal tissue inflammation, fibrosis, and progressive parenchymal damage.It represents a significant clinical challenge in veterinary medicine due to the lack of effective therapeutic options.Glutamate dehydrogenase 1 (GDH1), a key mitochondrial enzyme regulating amino acid metabolism, energy homeostasis, and redox balance, is linked to renal fibrosis via Reactive Oxygen Species (ROS) and profibrotic pathways, making it a plausible target for CON, while the role of GDH1 in animals with CON remains unclear.This study evaluates the role of GDH1 in obstructive renal injury via in vivo and in vitro models.The function of GDH1 was investigated in a neonatal rat model of partial unilateral ureteral obstruction (PUUO) and the potential mechanism was explored in an in vitro model.GDH1 expression was reduced in a neonatal rat model of PUUO.GDH1 overexpression alleviated renal fibrosis in PUUO-operated rats.TGF-1-treated rat renal tubular epithelial cells (NRK-52E) were employed as an in vitro model.Besides, GDH1 overexpression conferred protection against TGF-1-induced cellular damage, which was mediated by enhanced cell survival, reduced apoptosis, as well as the suppression of profibrotic marker expression.In conclusion, our study confirms GDH1-mediated protection conferring resistance against CON, highlighting GDH1 as a promising therapeutic target.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147894438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DOCK2 Deficiency Alleviates Murine Spinal Cord Ischemia-Reperfusion Injury via InhibitingAutophagy-Dependent Ferroptosis and the Modulatory Role of Sevoflurane Pretreatment","authors":"","doi":"10.29261/pakvetj/2025.295","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.295","url":null,"abstract":"Spinal cord ischemia-reperfusion injury (SCIRI) is a serious complication in veterinary practice, particularly following aortic cross-clamping during equine colic surgery, with no proven therapies for its neurological sequelae.Autophagy and ferroptosis drive SCIRI pathogenesis, but DOCK2's role remains unclear.We investigated DOCK2 using 110 male C57BL/6 wild-type (WT, n=6/group) and 6 DOCK2-deficient (DOCK2-KO) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-treated primary spinal neurons.Murine SCIRI was induced by clamping the abdominal aorta and spinal cord DOCK2 expression was increased post SCIRI, peaking at 24 h.DOCK2 deficiency also enhanced viability by 40% of primary spinal neurons under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions.SCIRI mice exhibited improved motor function recovery, reduced spinal cord pathological damage following DOCK2 knockdown.Mechanistically, we revealed that DOCK2 deficiency suppressed excessive ferroptosis-mediated by autophagy in vivo and in vitro.Notably, the protective effects of DOCK2 deficiency were abolished by autophagy activator rapamycin.Moreover, sevoflurane pretreatment exerted a protective effect against SCIRI, which was abrogated by DOCK2 overexpression.In conclusion, DOCK2 mediates SCIRI via autophagy-dependent ferroptosis and is a potential therapeutic target.Sevoflurane protects against SCIRI by inhibiting DOCK2, providing a basis for perioperative SCIRI management in animals.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147904299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional Analysis of c-di-AMP Metabolic Proteins in a Bovine-Pathogenic Bacilluscereus Isolate","authors":"","doi":"10.29261/pakvetj/2025.296","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.296","url":null,"abstract":"","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147905835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hycanthone inhibits African swine fever virus replication by inhibiting the cellular AKTphosphorylation and inducing viral DNA damage in porcine alveolar macrophage cultures","authors":"","doi":"10.29261/pakvetj/2025.228","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.228","url":null,"abstract":"African swine fever (ASF), caused by ASF virus (ASFV) infection, is a highly contagious and severe hemorrhagic viral disease with significant economic implications for the global pig farming industry.Currently, there are no effective vaccines or antiviral drugs available for controlling ASF epidemics.Developing effective strategies to combat this epidemic has become imperative.In this study, by screening a chemical library with 400 small molecule compounds, we identified that hycanthone, a previously used anthelminthic drug, exhibits the most potent inhibition on ASFV replication in PAMs, with an IC50 value of 0.57 mol/L.Hycanthone showed dose-dependent antiviral activity, reducing the mRNA levels of ASFV p30 and p72 proteins and decreasing viral DNA synthesis.Mechanistically, hycanthone attenuates ASFV replication by suppressing the cellular AKT phosphorylation and inducing viral DNA damage through interacting with ASFV AP endonuclease.Our findings suggest that hycanthone could serve as a promising therapeutic candidate for controlling ASFV infections.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147909141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reutilization of SKQ1's antibacterial and anti-quorum sensing activities to combatStreptococcus suis infection","authors":"","doi":"10.29261/pakvetj/2025.284","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.284","url":null,"abstract":"","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147915626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of PI3K/AKT Pathway Modulation Mediated by Oncostatin M (OSM) on theProliferation, Migration, and Extracellular Matrix Gene Expression of Donkey SkinFibroblasts","authors":"","doi":"10.29261/pakvetj/2025.271","DOIUrl":"https://doi.org/10.29261/pakvetj/2025.271","url":null,"abstract":"Donkeys exhibit a faster healing rate of dorsal skin wounds compared to their closely related counterparts, horses.This accelerated healing is accompanied by adequate collagen production without pathological over-deposition.However, studies exploring the underlying mechanisms of this superior wound healing in donkeys remain scarce.To explore the effects of OSM on the proliferation, migration, and extracellular matrix (ECM) gene expression of donkey skin fibroblasts, primary donkey skin fibroblasts were cultured and divided into four groups: OE-OSM, OE-NC, sh-OSM-2, and sh-NC.Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, and migration was evaluated through wound healing assays.Protein expression levels of collagen I (COL1), collagen III (COL3), and related factors were determined by Western blot (WB) analysis.Gene expression changes of COL1A1, COL3A1, Fibronectin (FN), and AKT Serine/threonine kinase 1 (AKT1) were quantified using RT-qPCR.Results indicated that OSM overexpression significantly reduced the proliferation and migration of donkey skin fibroblasts (P<0.01), while gene silencing produced opposite effects.Furthermore, overexpression of OSM notably reduced the expression levels of COL1A1, COL3A1, FN, and AKT1 (P<0.01), while simultaneously increasing Caspase-3 levels (P<0.01).These results suggest that OSM overexpression inhibits collagen synthesis (COL1 and COL3), reduces fibroblast proliferation and migration, and inhibits the PI3K/AKT signaling pathway.","PeriodicalId":19845,"journal":{"name":"Pakistan Veterinary Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.29261/pakvetj/2025.271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147902115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}