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Gentamicin, an aminoglycoside antibiotic, is a mixture of therapeutically active C1, C1a, C2 and other minor components. Despite its decades-long use in pigs and other species, its intramuscular (IM) pharmacokinetics/pharmacodynamics (PKs/PDs) are unknown in piglets. Furthermore, the PKs of many drugs differ between healthy and sick animals. Therefore, we investigated the PKs of gentamicin after a single IM dose (10 mg/kg) in healthy piglets and piglets that were intranasally co-infected with Actinobacillus pleuropneumoniae and Pasteurella multocida (PM). The plasma concentrations were measured using validated liquid chromatography/mass spectrometry. The gentamicin exposure was 36% lower based on the area under the plasma concentration–time curve and 16% lower based on the maximum plasma concentration (Cmax) in the infected piglets compared to the healthy piglets, while it was eliminated faster (shorter half-life and larger clearance) in the infected piglets compared to the healthy piglets. The clearance and volume of distribution were the highest for the C1 component. C1, C1a and C2 accounted for 22–25%, 33–37% and 40–42% of the total gentamicin exposure, respectively. The PK/PD target for the efficacy of aminoglycosides (Cmax/minimum inhibitory concentration (MIC) > 10) could be exceeded for PM, with a greater magnitude in the healthy piglets. We suggest integrating this PK information with antibiotic susceptibility data for other bacteria to make informed antibiotic and dosage regimen selections against piglet infections.

This research focuses on combating the increasing problem of antimicrobial resistance, especially in Escherichia coli (E. coli), by assessing the efficacy of aminoglycosides. The study specifically addresses the challenge of developing new therapeutic approaches by integrating experimental data with mathematical modeling to better understand the action of aminoglycosides. It involves testing various antibiotics like streptomycin (SMN), kanamycin (KMN), gentamicin (GMN), tobramycin (TMN), and amikacin (AKN) against the O157:H7 strain of E. coli. The study employs a pharmacodynamics (PD) model to analyze how different antibiotic concentrations affect bacterial growth, utilizing minimum inhibitory concentration (MIC) to gauge the effective bactericidal levels of the antibiotics. The study’s approach involved transforming bacterial growth rates, as obtained from time–kill curve data, into logarithmic values. A model was then developed to correlate these log-transformed values with their respective responses. To generate additional data points, each value was systematically increased by an increment of 0.1. To simulate real-world variability and randomness in the data, a Gaussian scatter model, characterized by parameters like κ and EC50, was employed. The mathematical modeling was pivotal in uncovering the bactericidal properties of these antibiotics, indicating different PD MIC (zMIC) values for each (SMN: 1.22; KMN: 0.89; GMN: 0.21; TMN: 0.32; AKN: 0.13), which aligned with MIC values obtained through microdilution methods. This innovative blend of experimental and mathematical approaches in the study marks a significant advancement in formulating strategies to combat the growing threat of antimicrobial-resistant E. coli, offering a novel pathway to understand and tackle antimicrobial resistance more effectively.

This study aimed to conduct a bioequivalence study of applying three pour-on ivermectin formulations at a dose of 1 mg/kg on the back of Korean native beef cattle (Hanwoo). To conduct bioequivalence testing, the pharmacokinetics of three groups (control Innovator, test Generic A, and test Generic B) of five clinically healthy Korean Hanwoo cattle (average weight 500 kg) were studied. After topical application to the skin, blood samples were drawn at the indicated times. These blood samples were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The time required to reach the maximum concentration (Tmax), the maximum concentration (Cmax), and the area under the curve (AUClast) of each pharmacokinetic parameter were compared for bioequivalence. The results showed that the control had a Tmax of 41 ± 1.24 h, a Cmax of 0.11 ± 0.01 μg/mL, and an AUClast of 9.33 ± 0 h*μg/mL). The comparator Generic A had a Tmax of 40 ± 1.14 h, a Cmax of 0.10 ± 0.01 (μg/mL, and an AUClast of 9.41 ± 0.57 h*μg/mL, while Generic B had a Tmax of 40 ± 2.21 h, a Cmax of 0.10 ± 0.01 μg/mL, and an AUClast of 9 h*μg/mL. The values of the bioequivalence indicators Cmax, Tmax, and AUC were all within the range of 80% to 120%, confirming that all three tested formulations were bioequivalent. In conclusion, the study showed that the two generic products were bioequivalent to the original product in Hanwoo cattle.

Novel swine orthopneumovirus (SOV) infections have been identified in pigs in the USA and some European countries but not in Asian countries, including South Korea, to date. The current study reports the first SOV infections in four domestic pig farms located in four provinces across South Korea. The detection rate of SOV in oral fluid samples using qRT-PCR was 4.4% (14/389), indicating the presence of the virus in pigs at commercial farms in Korea. Two complete genome sequences and one glycoprotein (G) gene sequence were obtained from SOV-positive samples. The complete genome analysis of KSOV-2201 and KSOV-2202 strains showed 98.2 and 95.4% homologies with a previously reported SOV, and the phylogenetic tree exhibited a high correlation with a previously reported SOV strain from the US and a canine pneumovirus (CPnV) strain from China. Based on the genetic analysis of the viral G gene, the murine pneumonia virus (MPV)-like orthopneumoviruses (MLOVs) were divided into two genogroups (G1 and G2). Seventeen CPnVs and two feline pneumoviruses were grouped into G1, while the Korean SOV strains identified in this study were grouped into G2 along with one SOV and two CPnVs. These results will contribute to expanding our understanding of the geographical distribution and genetic characteristics of the novel SOV in the global pig population.

Probiotics are being used as feed/food supplements as an alternative to antibiotics. It has been demonstrated that probiotics provide several health benefits, including preventing diarrhea, irritable bowel syndrome, and immunomodulation. Alongside probiotic bacteria-fermented foods, the different structural components, such as lipoteichoic acids, teichoic acids, peptidoglycans, and surface-layer proteins, offer several advantages. Probiotics can produce different antimicrobial components, enzymes, peptides, vitamins, and exopolysaccharides. Besides live probiotics, there has been growing interest in consuming inactivated probiotics in farm animals, including pigs. Several reports have shown that live and killed probiotics can boost immunity, modulate intestinal microbiota, improve feed efficiency and growth performance, and decrease the incidence of diarrhea, positioning them as an interesting strategy as a potential feed supplement for pigs. Therefore, effective selection and approach to the use of probiotics might provide essential features of using probiotics as an important functional feed for pigs. This review aimed to systematically investigate the potential effects of lactic acid bacteria in their live and inactivated forms on pigs.

Employing affordable and uncomplicated sample preparation techniques to recommend the most efficient antibacterial therapy could help reduce antibiotic-resistant bacteria. This study evaluated the suitability of immunoassays and microbiological assays as alternatives for liquid chromatography/mass spectrometry (LC/MS) in determining plasma tylosin concentrations after intramuscular administration at a dose of 20 mg/kg to both healthy and diseased pigs in clinical veterinary practice. The diseased pigs were confirmed using the target genes Actinobacillus pleuropneumoniae (apxIVA) and Pasteurella multocida (kmt1). The methods showed good linearity, precision, and accuracy. In both healthy and diseased pigs, a significant correlation was observed between LC/MS and the microbiological assay (Pearson correlation coefficient: 0.930, p < 0.001 vs. Pearson correlation coefficient: 0.950, p < 0.001) and between LC/MS and the enzyme-linked immunosorbent assay (ELISA) (Pearson correlation coefficient: 0.933; p < 0.001 vs. Pearson correlation coefficient: 0.976, p < 0.001). A strong correlation was observed between the microbiological assay and the ELISA in both healthy and diseased pigs (Pearson correlation coefficient: 0.911; p < 0.001 vs. Pearson correlation coefficient: 0.908, p < 0.001). A Bland-Altman analysis revealed good agreement between the methods, i.e., 95% of the differences were within the limits of agreement. Therefore, the microbiological assay and the ELISA, which demonstrated sufficient precision and accuracy, can be viable alternatives to LC/MS when it is unavailable.

We isolated and characterized Limosilactobacillus reuteri PSC102 and evaluated its probiotic, antioxidant, and antibacterial properties. We preliminarily isolated 154 candidates from pig feces and analyzed their Gram nature, morphology, and lactic acid production ability. Based on the results, we selected eight isolates and tested their ability to produce digestive enzymes. Finally, we identified one isolate using 16S rRNA gene sequencing, namely, L. reuteri PSC102. We tested its probiotic properties in vitro, including extracellular enzyme activities, low pH and bile salt tolerance, autoaggregation and coaggregation abilities, adhesion to Caco-2 cells, antibiotic susceptibility, and hemolytic and gelatinase activities. Antioxidant activity was determined using 1-diphenyl-2-picrylhydrazyl and 2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical scavenging and reducing power assays. The antibacterial activity of this strain and its culture supernatant against enterotoxigenic Escherichia coli were evaluated using a time-kill assay and disk diffusion method, respectively. L. reuteri PSC102 exhibited tolerance toward low pH and bile salt and did not produce harmful enzymes or possess hemolytic and gelatinase activities. Its intact cells and cell-free extract exhibited potential antioxidant activities, and significantly inhibited the growth of enterotoxigenic E. coli. Our results demonstrate that L. reuteri PSC102 is a potential probiotic candidate for developing functional feed.

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity properties of E. cava 70% ethanol extract. To evaluate the anti-obesity effect of E. cava, both in vitro and in vivo tests were performed. E. cava suppresses pre-adipocyte 3T3-L1 differentiation in a dose-dependent manner. In HFD-induced obese rats’ models, administration of E. cava 125, 250, and 500 mg/kg significantly decreases total body weight and organs, especially liver weight, in all treatment groups. Adipose tissue weight, including subcutaneous, epididymal, peritoneal, and mesenteric adipose tissue, was markedly reduced in E. cava-treated HFD rats in dose-dependent manners. In addition, liver-related biomarkers AST, ALP, ALT, and GGT were evaluated; the lower level of liver-related biomarkers indicates no liver injury or fatty liver issue in E. cava HFD treatment groups. In addition, E. cava treatment has significant effects on the expression of adipogenic and lipogenic (PPAR-γ, FAS, LPL, and SREBP-1c) genes. Altogether, these results show the anti-obesity effect of E. cava. We concluded that E. cava could be a potential candidate for the prevention of obesity-induced by a high-fat diet.

This study aimed to optimize the colistin-based antibacterial therapy to prevent antimicrobial resistance related to biofilm formation in avian pathogenic Escherichia coli (APEC) in chicken. Of all the bacterial isolates (n = 136), 69 were identified as APEC by polymerase chain reaction (PCR). Through a series of antibiotic susceptibility tests, susceptibility to colistin (50 concentration (1.00 μg/mL), and regrowth was not inhibited even during multiple exposures. However, upon exposure to 8 μg/mL—a concentration that was close to the MPC—the growth of APEC was inhibited, including in the resistant strains. Additionally, colistin-induced resistant strains showed a slower growth compared with the susceptible ones. Colistin-induced resistant APEC strains did not show colistin resistance gene (mcr-1). However, the expression of higher mgrB and phoQ levels was observed in the resistant strains. Furthermore, these strains showed increased formation of biofilm. Hence, the present study indicated that colistin could induce resistance through the increased formation of biofilm in APEC strains by enhancing the expression of phoQ.

Chronic alcohol consumption can cause hepatic injury and alcohol-induced toxicities. Extracts from Smilax china root have been widely used in traditional medicine and for their potential pharmacological benefits. We aimed to determine if fermented Smilax china extract (FSC) regulates alcoholic fatty liver and liver injury using two in vivo experiments. Sprague-Dawley rats were administered ethanol (3 g/kg b.w.; po) with or without FSC pretreatment to induce an acute hangover. In another experiment, rats were fed either a normal or Lieber-DeCarli ethanol (6.7%) diet with or without FSC pretreatment (125, 250, and 500 mg/kg b.w.; po) for 28 days. Serum biomarkers, liver histopathology, and the mRNA levels of anti-inflammatory, antioxidant, lipogenic, and lipolytic genes were analyzed. FSC pretreatment significantly reduced blood alcohol and acetaldehyde concentrations, upregulated the mRNA expression of alcohol dehydrogenase, aldehyde dehydrogenase, and superoxide dismutase, and decreased the activities of liver enzymes in a dose-dependent manner. It also downregulated SERBP-1c and upregulated PPAR-α and reduced the gene expression of the anti-inflammatory cytokine IL-6 in the liver. The final extract after fermentation had increased GABA content. Furthermore, FSC was found to be safe with no acute oral toxicity in female rats. Thus, FSC increases alcohol metabolism and exhibits antioxidant and anti-inflammatory effects to induce hepatoprotection against alcohol-induced damage. It may be used as a functional food ingredient after excess alcohol consumption.

This research aimed to assess the pharmacokinetics/pharmacodynamics (PK/PD) and tissue residues of spiramycin in chickens. The PK of spiramycin were determined in 12 chickens using a parallel study design in which each group of chickens (n = 6) received a single dose of spiramycin at 17 mg/kg intravenously (IV) or orally. Plasma samples were collected at assigned times for up to 48 h to measure spiramycin concentrations. Additionally, a tissue depletion study was performed in 42 chickens receiving spiramycin at 17 mg/kg/day orally for 7 days. The area under the plasma concentration–time curve values were 29.94 ± 4.74 and 23.11 ± 1.83 µg*h/mL after IV and oral administrations, respectively. The oral bioavailability was 77.18%. The computed withdrawal periods of spiramycin were 11, 10, and 7 days for liver, muscle, and skin and fat, respectively. The minimum inhibitory concentration for spiramycin against Mycoplasma synoviae (M. synoviae) strain 1853 was 0.0625 µg/mL. Using the PK/PD integration, the appropriate oral dose of spiramycin against M. synoviae was estimated to be 15.6 mg/kg. Thus, we recommend an oral dose of 15.6 mg spiramycin/kg against M. synoviae in chickens and a withdrawal period of 11 days following oral treatment with 17 mg spiramycin/kg/day for 7 days.

The present study aimed to assess the immunomodulatory effects of fermented Aronia melanocarpa extract (FAME) on RAW 264.7 cells and BALB/c mice. Aronia melanocarpa fruit was fermented with Lactobacillus plantarum EJ2014 by adding yeast extract and monosodium glutamate for 9 days at 30 °C to produce γ-aminobutyric acid (GABA). After fermentation, significant GABA production was noted, along with minerals, polyphenols, and flavonoids (p < 0.05). The polyphenol content was confirmed by liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis. RAW 264.7 cells were stimulated with lipopolysaccharide (LPS, 1 μg/mL) in the presence or absence of FAME, and proinflammatory cytokine contents were measured by qPCR. In the in vivo experiment, female BALB/c mice were administered 125, 250, and 500 mg/kg of FAME for 21 days. FAME treatment increased neutrophil migration and phagocytosis (p < 0.05). It also increased splenocyte proliferation, CD4+ and CD8+ T-cell expression, and lymphocyte proliferation. Furthermore, it increased IFN-γ, IL-2, and IL-4 cytokine levels in a dose-dependent manner (p < 0.05). However, it decreased TNF-α and IL-6 levels (p < 0.05). These results indicate that FAME fortified with GABA including bioactive compounds exerts anti-inflammatory effects by inhibiting proinflammatory cytokines in RAW 264.7 cells and modulates immune response in mice. Thus, FAME could be a potential therapeutic agent for inflammatory disorders.

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (p < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

The leaves of Homalomena aromatica are traditionally used in Bangladesh for the treatment of different chronic ailments. The purpose of this study was to explore in vitro antioxidant, thrombolytic activities, and in vivo neuropharmacological effects of methanolic extract of Homalomena aromatica (MEHA) leaves. Antioxidant activity of MEHA was assessed by a DPPH free radical scavenging assay and total phenolics content, total flavonoids content were also measured. The thrombolytic activity was determined by percentage of clot lysis and neuropharmacological activities by hole board, tail suspension, forced swimming and elevated plus maze tests. The results showed that the IC50 value of the extract against DPPH was 199.51 μg/mL. Quantitative analysis displayed higher contents of phenolics and flavonoids (147.71 mg gallic acid equivalent/g & 66.65 mg quercetin equivalent/g dried extract, respectively). The extract also showed a significant clot lysis (33.31%) activity. In case of anxiolytic activity, the elevate plus maze (EPM) test demonstrated an increase in time spent in open arms, and in case of hole board test, the number of head dipping was also significantly increased (p < 0.05). All the test compared with control (1% Tween in water) and standard (diazepam 1 mg/kg), significant dose (200 & 400 mg/kg) dependent anxiolytic activity was found. In antidepressant activity, there was a significant decrease in period of immobility in both test models (tail suspension and forced swimming) (p < 0.05). Moreover, 13 compounds were identified as bioactive, showed good binding affinities to xanthine oxidoreductase, tissue plasminogen activator receptor, potassium channel receptor, human serotonin receptor targets in molecular docking experiments. Furthermore, ADME/T analysis revealed their drug-likeness, likely pharmacological actions and non-toxic upon consumption. Taken together, our finding support the traditional medicinal use of this plant, which may provide a potential source for future drug discovery.

Atopic dermatitis (AD) is an allergic and chronic inflammatory skin disease. The present study investigates the anti-allergic, antioxidant, and anti-inflammatory activities of the ethanolic extract of Cornus officinalis (COFE) for possible applications in the treatment of AD. COFE inhibits the release of β-hexosaminidase from RBL-2H3 cells sensitized with the dinitrophenyl-immunoglobulin E (IgE-DNP) antibody after stimulation with dinitrophenyl-human serum albumin (DNP-HSA) in a concentration-dependent manner (IC50 = 0.178 mg/mL). Antioxidant activity determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power assay, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, result in EC50 values of 1.82, 10.76, and 0.6 mg/mL, respectively. Moreover, the extract significantly inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the mRNA expression of iNOS and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) through attenuation of NF-κB activation in RAW 264.7 cells. COFE significantly inhibits TNF-α-induced apoptosis in HaCaT cells without cytotoxic effects (p < 0.05). Furthermore, 2-furancarboxaldehyde and loganin are identified by gas chromatography/mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, respectively, as the major compounds. Molecular docking analysis shows that loganin, cornuside, and naringenin 7-O-β-D-glucoside could potentially disrupt the binding of IgE to human high-affinity IgE receptors (FceRI). Our results suggest that COFE might possess potential inhibitory effects on allergic responses, oxidative stress, and inflammatory responses.