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Acute renal failure is a common clinical disease in canines, affecting antioxidant levels and decreasing the body's resistance. This study aims to explore the therapeutic mechanism of Nano-selenium in acute renal failure. The histopathological and imaging changes of kidney tissue were observed with the gene and protein expression levels of Keap1, Nrf2, HO-1, and NQO1 in the kidney. According to our findings, adding nano-selenium can effectively reduce the concentration of CRE and BUN in blood and kidney tissues. It increased the activity of GSH-PX and SOD by an effective reduction of MDA. Through pathological and imaging observations, it was found that adding nano-selenium could improve the kidney tissue structure of acute renal failure. The results of the RT-qPCR experiment showed that after the addition of nano-selenium, the mRNA expression of the Keap1 gene decreased significantly. In contrast, the mRNA expression of the Nrf2, HO-1, and NQO1 genes increased significantly. The experimental results were further verified by western blot and immunohistochemical analysis. Hence, the nano-selenium intervention improved kidney function and increased antioxidant levels in canines suffering from acute renal failure with the involvement of the Keap1-Nrf2/ARE signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Biofilms, such as those from Staphylococcus epidermidis , are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection., Objectives: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation., Methods: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied., Results: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis . In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production., Conclusions: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated . Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

In this study, enrofloxacin (ENR) was encapsulated by oxidized hyaluronic acid (OHA) containing aldehyde groups and chitosan oligosaccharide (COS) containing amino groups through Schiff's base reaction to achieve on-demand release in the micro-environment (pH 5.5 and HAase) of bacterial-infected wounds (Escherichia coli and Staphylococcus aureus). The formation mechanism, physicochemical characterization, responsive release performance, in vitro and in vivo antimicrobial activities, and in vivo regeneration in full-thickness wounds in a bacterial-infected mouse model of the ENR nanogels were systematically studied. According to the single-factor experiment and Design-Expert software, the optimized formula was 3.8 mg/ml COS, 0.5 mg/ml OHA, and 0.3 mg/ml ENR, respectively. The mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 35.6 ± 1.7 nm, -6.7 ± 0.5 mV, 0.25 ± 0.02, 30.4 % ± 1.3 %, and 76.3 % ± 2.6 %, respectively. The appearance, optical microscopy images, SEM, TEM, PXRD, and FTIR showed that the ENR nanogels were successfully prepared. The ENR nanogels exhibited obvious pH and HAase-responsiveness by swelling ratios and in vitro release and had stronger antibacterial activity with time-dependent and concentration-dependent effects, as well as accelerating infected wound healing. In vitro and in vivo biosafety studies suggested the great promise of ENR nanogels as biocompatible wound dressings for infected wounds., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brucellosis is considered one of the most hazardous zoonotic diseases all over the world. It causes formidable economic losses in developed and developing countries. Despite the significant attempts to get rid of Brucella pathogens in many parts of the world, the disease continues to spread widely. Recently, many attempts proved to be effective for the prevention and control of highly contagious bovine brucellosis, which could be followed by others to achieve a prosperous future without rampant Brucella pathogens. In this study, the updated view for worldwide Brucella distribution, possible predisposing factors for emerging Brucella pathogens, immune response and different types of Brucella vaccines, genomics and proteomics approaches incorporated recently in the field of brucellosis, and future perspectives for prevention and control of bovine brucellosis have been discussed comprehensively. So, the current study will be used as a guide for researchers in planning their future work, which will pave the way for a new world without these highly contagious pathogens that have been infecting and threatening the health of humans and terrestrial animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dawood, Elrashedy, Nayel, Salama, Guo, Zhao, Algharib, Zaghawa, Zubair, Elsify, Mousa and Luo.)

The main goal of the current report is to assess the protective impacts of chia seeds against obesity-induced ovarian dysfunctions with a trial to elucidate the mechanism of action. Forty rats were divided into 4 groups including lean untreated, lean consuming chia seeds, obese untreated, and rats consumed high-fat diet (HFD) mixed with ground chia seeds for 10 weeks. Anthropometric measures including visceral fat, peri-ovarian fat, ovarian weights, and duration of the estrous cycle were computed. Serum luteinizing (LH), follicular stimulating (FSH), progesterone, estradiol hormones, and tumor necrosis-α (TNF-α) were estimated. Ovarian histopathology and immunohistochemistry (CD31) were performed. Results showed that chia seeds clearly reduced obesity and induced alteration in anthropometric measures with a clear increase in LH and progesterone. Such seeds notably reversed histopathological alteration and reduced TNF-α, and CD31 induced by HFD. Conclusively, chia seeds have a potential protective role against obesity-induced ovarian dysfunction owing to their anti-inflammatory properties., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In order to overcome the treatment difficulty of Lawsonia intracellularis (L.intracellularis) using antibiotics, the tilmicosin (TIL)-loaded sodium alginate (SA)/gelatin composite nanogels modified with bioadhesive substances were designed. The optimized nanogels were prepared by electrostatic interaction between SA and gelatin at a mass ratio of 1:1 and CaCl 2 as an ionic crosslinker and further modified with guar gum (GG). The optimized TIL-nanogels modified with GG had a uniform spherical shape with a diameter of 18.2 ± 0.3 nm, LC of 29.4 ± 0.2 %, EE of 70.4 ± 1.6 %, PDI of 0.30 ± 0.04, and ZP of -32.2 ± 0.5 mv. The FTIR, DSC, and PXRD showed that GG was covered on the surface of TIL-nanogels in a pattern of staggered arrangements. The TIL-nanogels modified with GG had the strongest adhesive strength amongst those with I-carrageenan and locust bean gum and the plain nanogels, and thus significantly enhanced the cellular uptake and accumulation of TIL via clathrin-mediated endocytosis. It exhibited an increased therapeutic effect against L.intracellularis in vitro and in vivo. This study will provide guidance for developing nanogels for intracellular bacterial infection treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As a novel strategy for in vivo visualization tracking and monitoring, carbon dots (CDs) emitting long wavelengths (LW, 600-950 nm) have received tremendous attention due to their deep tissue penetration, low photon scattering, satisfactory contrast resolution and high signal-to-background ratios. Although, the mechanism of CDs emitting LW remains controversial and what properties are best for in vivo visualization have not been specifically elucidated, it is more conducive to the in vivo application of LW-CDs through rational design and ingenious synthesis based on the appreciation of the luminescence mechanism. Therefore, this review analyzes the current tracer technologies applied in vivo and their advantages and disadvantages, with emphasis on the physical mechanism of emitting LW fluorescence for in vivo imaging. Subsequently, the general properties and merits of LW-CDs for tracking and imaging are summarized. More importantly, the factors affecting the synthesis of LW-CDs and its luminescence mechanism are highlighted. Simultaneously, the application of LW-CDs for disease diagnosis, integration of diagnosis and therapy are summarized. Finally, the bottlenecks and possible future directions of LW-CDs in visualization tracking and imaging in vivo are detailly discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background This study aimed to improve the sustained and controlled release of glycyrrhizic acid to the infected site of Staphylococcus aureus small colony variants (SCVs). Methods The glycyrrhizic acid-loaded chitosan composite nanogel was prepared by inclusion action, Schiff's base formation, and electrostatic action. Furthermore, the formulation screening, characteristics, in vitro release, and antibacterial activity of the glycyrrhizic acid composite nanogel were explored. Results The final optimal formula comprised 10 mg/mL (chitosan) and 50 μL (glutaraldehyde). The loading capacity, encapsulation efficiency, mean size, polydispersity index, and zeta potential were 8.8%±1.6%, 92.1%±2.8%, 478.3±2.8 nm, 0.37±0.10, and 25.3±3.6 mv, respectively. Scanning electron microscope images showed a spherical shape with a relatively uniform distribution. The in vitro release study showed that glycyrrhizic acid composite nanogel exhibited a biphasic pattern with a sustained release of 52.1%±2.0% at 48 h in the pH 5.5 PBS. The minimum inhibitory and minimum biofilm inhibitory concentrations of glycyrrhizic acid composite nanogel against SCVs were 0.625 μg/mL. The time-killing curves and live/dead bacterial staining showed that glycyrrhizic acid composite nanogel had a stronger curative effect against SCVs strain with concentration-dependent. Conclusion This study provides promising glycyrrhizic acid composite nanogel to improve the treatment of SCV infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The development of nanogels has become an attractive strategy to enhance the antibacterial activity performance of bacteria., Methods: The ciprofloxacin composite nanogels were successfully prepared by electrostatic interaction between gelatin (positive charge) and CMC (negative charge) with the help of sodium tripolyphosphate (TPP) as ionic crosslinkers, to increase the antibacterial activity of ciprofloxacin against Staphylococcus aureus (S. aureus) mastitis infection. The formulation screening, characterization, in vitro release, antibacterial activity, and biosafety were studied., Results: The optimized formulation was fabricated of 20 mg/mL (CMC) and 50mg/mL (gelatin). The optimized ciprofloxacin composite nanogels were homogenous canary yellow suspension with a sedimentation rate of 1 and were incorporated in nano-sized cross-linked polymeric networks. The particle sizes were distributed as, 402.7±1.3 nm, PDI of 0.12±0.01, ZP of -24.5±0.2mv, EE of 74.28%±0.03%, LC of 20.5%±0.05%. Scanning electron microscope images revealed that ciprofloxacin might be incorporated in nano-sized cross-linked polymeric networks. Fourier transform infrared showed that the spontaneous electrostatic interactions between CMC and gelatin produce the network structure and form the composite nanogels. Meanwhile, in vitro release study showed that ciprofloxacin composite nanogels had sustained-release performances. The ciprofloxacin composite nanogels had shown better antibacterial activity against SCV 102 isolate than S. aureus ATCC 29213 and S. aureus 101isolates. The biosafety studies suggested the great promise of the injectable ciprofloxacin composite nanogels as a biocompatible breast injection., Conclusion: This study will afford a potential approach for developing injectable ciprofloxacin-loaded gelatin-CMC composite nanogels for cow S. aureus mastitis therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The stomach acid degradation, mucus clearance and intestinal epithelial impermeability severely limit the oral delivery of polypeptide drugs. To simultaneously address the three major barriers, novel self-assembled core-shell nanosystems (CA-NPs) were designed. The fabricated shell of citric acid cross-linked carboxymethyl cellulose (CA-CMC) wrapped on core nanoparticles (HA-NPs) maintained the integrity of CA-NPs in the stomach. When CA-NPs passed through the stomach, the CA-CMC shell was gradually degraded to release the core HA-NPs in the intestine. HA-NPs with numerous hydrophilic groups and mannose side chains rapidly penetrated through the mucus layer and efficiently transcellular transported via the glucose transporter (GLUT)-mediated and paracellular transport through reversible opening of tight junctions (TJs) by CA-CMC. The oral bioavailability and therapeutic effects of CA-NPs-loaded polypeptide colistin against Escherichia coli (E. coli) bacteremia in mice were significantly increased compared with the native colistin, respectively. Good safety was observed following oral daily delivery for 14 consecutive days. Thus, CA-NPs may offer a promising strategy for the oral delivery of polypeptide drugs., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2022. Published by Elsevier B.V.)

Enrofloxacin has a poor palatability and causes strong gastric irritation; the oral formulation of enrofloxacin is unavailable, which limits the treatment of Escherichia coli ( E. coli ) infections via oral administration. To overcome the difficulty in treating intestinal E. coli infections, an oral intelligent-responsive chitosan-oligosaccharide (COS)-sodium alginate (SA) composite core-shell nanogel loaded with enrofloxacin was explored. The formulation screening, characteristics, pH-responsive performance in gastric juice and the intestinal tract, antibacterial effects, therapeutic effects, and biosafety level of the enrofloxacin composite nanogels were investigated. The optimized concentrations of COS, SA, CaCl 2 , and enrofloxacin were 8, 8, 0.2, and 5 mg/mL, respectively. The encapsulation efficiency, size, loading capacity, zeta potential, and polydispersity index of the optimized formulation were 72.4 ± 0.8%, 143.5 ± 2.6 nm, 26.6 ± 0.5%, -37.5 ± 1.5 mV, and 0.12 ± 0.07, respectively. Scanning electron microscopy images revealed that enrofloxacin-loaded nanogels were incorporated into the nano-sized cross-linked networks. Fourier transform infrared spectroscopy showed that the nanogels were prepared by the electrostatic interaction of the differently charged groups (positive amino groups (-NH 3 + ) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted "on-demand" release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against - ) of SA). In vitro, pH-responsive release performances revealed effective pH-responsive performances, which can help facilitate targeted "on-demand" release at the target site and ensure that the enrofloxacin has an ideal stability in the stomach and a responsive release in the intestinal tract. The antibacterial activity study demonstrated that more effective bactericidal activity against E. coli could have a better treatment effect than the enrofloxacin solution. Furthermore, the enrofloxacin composite nanogels had great biocompatibility. Thus, the enrofloxacin composite core-shell nanogels might be an oral intelligent-responsive preparation to overcome the difficulty in treating intestinal bacterial infections.

Background: Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis., Objectives: In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites., Methods: The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied., Results: The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 µg/mL, respectively. The time-killing curves and live-dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver., Conclusions: Florfenicol composite nanogels might improve the treatment of SCV infections., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Korean Society of Veterinary Science.)

The use of nano-sized materials is increasingly growing, while consequent health and environmental risks are still disputed. On the other hand, plant extracts have been reported to improve fish general health status and enhance antioxidant capacity. Thus, the present study was aimed to assess potential effects of Allium hirtifolium extract (AHE) to fortify antioxidant responses of Common carp (Cyprinus carpio) exposed to foodborne Zinc oxide nanoparticles (ZnO-NPs). Five hundred and forty fish were randomly allocated into 18 tanks and received six diets including a basal diet (as control), basal diet incorporated with either 13 mg/kg (ZnO-25) or 26 mg/kg (ZnO-50) of ZnO-NPs, 1.5% AHE (AHE-1.5), and similar concentrations of ZnO-NPs plus AHE (ZnO-25-AHE) and (ZnO-50-AHE) for a period of 30 days. Results revealed that blood indices, stress biomarkers (glucose and cortisol), and antioxidant parameters and genes in AHE-1.5 group were significantly modulated and improved when compared to other groups (P < 0.05). In AHE-enriched groups, serum and liver tissue antioxidative parameters were enhanced as reflected in a noticeable decrease in malondialdehyde value and an increase in catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. However, current results showed that diets incorporated with ZnO-NPs elevated the stress parameters besides a significant reduction for most measured biochemical parameters and AHE supplementation ameliorated these effects in terms of improving antioxidant parameters. In ZnO-25-AHE, and ZnO-50-AHE, the values for expression of GPx were found significantly (P < 0.05) different from that of ZnO-25 and ZnO-50. On the contrary, SOD showed a non-significant difference (P > 0.05) among control, ZnO-25, and ZnO-50-AHE, also in-between ZnO-25 and ZnO-25-AHE. The present results indicate that AHE supplementation could trigger antioxidant responses both at tissue and molecular levels suggesting its outstanding protective effects against foodborne toxicity of ZnO-NPs in Common carp., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present experiment investigated the potential protective role of parsley ( Petroselinum crispum ) seed meal (PSM) in alleviating methomyl (MET)-adverse impacts on growth, whole-body composition, hematological indicators, hepatorenal function, immune response, oxidative status, and disease resistance to Pseudomonas aeruginosa . For this purpose, 225 healthy Nile tilapia ( Oreochromis niloticus ) were allotted into five groups (45 fish/group in triplicate). One group was reared in clean water and fed a non-supplemented basal diet, while the other groups were exposed to 20.39 μg L -1 MET and fed a non-fortified basal diet or basal diets supplemented with 0.5, 1.0, or 2.0% of PSM for 60 days. The obtained data revealed significantly lower weight gain, feed intake, and specific growth rate, but higher feed conversion ratio and decreases in crude protein, lipid, and ash contents in the MET-exposed fish. Anemia, leukopenia, lymphocytopenia, and esonipenia were also obvious. Furthermore, MET-exposed fish had significantly higher serum levels of hepatic enzymes and renal damage products. Nevertheless, there was a significant depletion of enzymatic and non-enzymatic antioxidants and increased malondialdehyde, myeloperoxidase, and tumor necrosis factor-α levels in MET-exposed fish. The MET exposure significantly depressed lysozyme activity, nitric oxide, complement3, acetylcholinesterase activity, total proteins, globulin, and albumin levels in O. niloticus serum. Furthermore, pathological alterations in the liver and kidney were noted. The relative percentage of survival rate in MET-exposed fish was dramatically reduced on day 14 post-challenge with P. aeruginosa . The inclusion of PSM, on the other hand, greatly alleviated most of the MET-related negative effects. Taken together, the dietary intervention with PSM has a promising role in alleviating MET-deleterious impacts, rendering parsley seeds a viable aqua feed additive for O. niloticus .

Mycoplasmas as economically important and pantropic pathogens can cause similar clinical diseases in different hosts by eluding host defense and establishing their niches despite their limited metabolic capacities. Besides, enormous undiscovered virulence has a fundamental role in the pathogenesis of pathogenic mycoplasmas. On the other hand, they are host-specific pathogens with some highly pathogenic members that can colonize a vast number of habitats. Reshuffling mycoplasmas genetic information and evolving rapidly is a way to avoid their host's immune system. However, currently, only a few control measures exist against some mycoplasmosis which are far from satisfaction. This review aimed to provide an updated insight into the state of mycoplasmas as pathogens by summarizing and analyzing the comprehensive progress, current challenge, and future perspectives of mycoplasmas. It covers clinical implications of mycoplasmas in humans and domestic and wild animals, virulence-related factors, the process of gene transfer and its crucial prospects, the current application and future perspectives of nanotechnology for diagnosing and curing mycoplasmosis, Mycoplasma vaccination, and protective immunity. Several questions remain unanswered and are recommended to pay close attention to. The findings would be helpful to develop new strategies for basic and applied research on mycoplasmas and facilitate the control of mycoplasmosis for humans and various species of animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dawood, Algharib, Zhao, Zhu, Qi, Delai, Hao, Marawan, Shirani and Guo.)

Background: The poor intracellular concentration of enrofloxacin might lead to treatment failure of cow mastitis caused by Staphylococcus aureus small colony variants (SASCVs)., Objectives: In this study, enrofloxacin composite nanogels were developed to increase the intracellular therapeutic drug concentrations and enhance the efficacy of enrofloxacin against cow mastitis caused by intracellular SASCVs., Methods: Enrofloxacin composite nanogels were formulated by an electrostatic interaction between gelatin (positive charge) and sodium alginate (SA; negative charge) with the help of CaCl 2 (ionic crosslinkers) and optimized by a single factor test using the particle diameter, zeta potential (ZP), polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) as indexes. The formation mechanism, structural characteristics, bioadhesion ability, cellular uptake, and the antibacterial activity of the enrofloxacin composite nanogels against intracellular SASCVs strain were studied systematically., Results: The optimized formulation was comprised of 10 mg/mL (gelatin), 5 mg/mL (SA), and 0.25 mg/mL (CaCl 2 ). The size, LC, EE, PDI, and ZP of the optimized enrofloxacin composite nanogels were 323.2 ± 4.3 nm, 15.4% ± 0.2%, 69.6% ± 1.3%, 0.11 ± 0.02, and -34.4 ± 0.8 mV, respectively. Transmission electron microscopy showed that the enrofloxacin composite nanogels were spherical with a smooth surface and good particle size distributions. In addition, the enrofloxacin composite nanogels could enhance the bioadhesion capacity of enrofloxacin for the SASCVs strain by adhesive studies. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration were 2, 4, 4, and 8 μg/mL, respectively. The killing rate curve had a concentration-dependent bactericidal effect as increasing drug concentrations induced swifter and more radical killing effects., Conclusions: This study provides a good tendency for developing enrofloxacin composite nanogels for treating cow mastitis caused by intracellular SASCVs and other intracellular bacterial infections., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Korean Society of Veterinary Science.)

Currently, the intervention of plant by-products in the fish diet has gained tremendous attention owing to the economic and high nutritious value. The current study is a pioneer attempt to incorporate the apricot, Prunus armeniaca kernel powder (PAKP) into the Common carp, Cyprinus carpio diets, and assess its efficacy on growth, digestion, intestinal morphology, immunity, antioxidant capacity, and splenic cytokines expression, besides the antibacterial role against Aeromonas veronii infection. Apparently healthy fish (N = 120) with an initial body weight of 24.76 ± 0.03g were allotted in 12 glass aquaria (60 L) and randomly distributed into four groups (triplicates, 10 fish/aquarium). The control group (PAKP0) was fed a basal diet without additives. The second, third, and fourth groups were provided PAKP diets with various concentrations (2.5 (PAKP2.5), 5 (PAKP5), and 10 g kg -1 (PAKP10)) respectively. After 60 days (feeding trial), sub-samples of the fish (12 fish/group) were intraperitoneally injected with 1 × 10 7  CFU mL -1 of A. veronii. Results revealed that body weight gain, feed conversion ratio, and specific growth rates were significantly augmented in the PAKP10 group in comparison to the other groups. The dietary inclusion of PAKP at all concentrations boosted the digestive capacity and maintained the intestinal morphology (average villus length, villus width, and goblet cells count) with a marked improvement in PAKP10. Moreover, fish fed on PAKP10 followed by PAKP5 then PAKP2.5 diets had noticeably elevated values of immunological biomarkers (IgM, antiprotease, and lysozyme activity) and antioxidant capabilities (the total antioxidant capacity, superoxide dismutase, and reduced glutathione) as well as significant up-regulation of immune and antioxidant-related genes (TGF-β2, TLR-2, TNF-α, IL-10, SOD, GPx, and GSS). Fourteen days post-infection with A. veronii, the highest relative percentage survival of fish was observed in PAKP10 (83.33%), followed by PAKP5 (66.67%), and PAKP2.5 (50%). Our results indicated that a dietary intervention with PAKP could promise growth, digestion, immunity, and protect C. carpio against A. veronii infection in a dose-dependent manner. This offers a framework for future application of such seeds as a growth promotor, immune-stimulant, and antioxidant, besides an alternative cheap therapeutic antibacterial agent for sustaining the aquaculture industry., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The poor bioadhesion capacity of tilmicosin resulting in treatment failure for Staphylococcus aureus small colony variants (SASCVs) mastitis., Objectives: This study aimed to increase the bioadhesion capacity of tilmicosin for the SASCVs strain and improve the antibacterial effect of tilmicosin against cow mastitis caused by the SASCVs strain., Methods: Tilmicosin-loaded chitosan oligosaccharide (COS)-sodium carboxymethyl cellulose (CMC) composite nanogels were formulated by an electrostatic interaction between COS (positive charge) and CMC (negative charge) using sodium tripolyphosphate (TPP) (ionic crosslinkers). The formation mechanism, structural characteristics, bioadhesion, and antibacterial activity of tilmicosin composite nanogels were studied systematically., Results: The optimized formulation was comprised of 50 mg/mL (COS), 32 mg/mL (CMC), and 0.25 mg/mL (TPP). The size, encapsulation efficiency, loading capacity, polydispersity index, and zeta potential of the optimized tilmicosin composite nanogels were 357.4 ± 2.6 nm, 65.4 ± 0.4%, 21.9 ± 0.4%, 0.11 ± 0.01, and -37.1 ± 0.4 mV, respectively; the sedimentation rate was one. Scanning electron microscopy showed that tilmicosin might be incorporated in nano-sized crosslinked polymeric networks. Moreover, adhesive studies suggested that tilmicosin composite nanogels could enhance the bioadhesion capacity of tilmicosin for the SASCVs strain. The inhibition zone of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels were 2.13 ± 0.07, 3.35 ± 0.11, and 1.46 ± 0.04 cm, respectively. The minimum inhibitory concentration of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels against the SASCVs strain were 2, 1, and 1 µg/mL, respectively. The in vitro time-killing curves showed that the tilmicosin composite nanogels increased the antibacterial activity against the SASCVs strain., Conclusions: This study provides a potential strategy for developing tilmicosin composite nanogels to treat cow mastitis caused by the SASCVs strain., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Korean Society of Veterinary Science.)

Physiologically based pharmacokinetic (PBPK) models have become important tools for the development of novel human drugs. Food-producing animals and pets comprise an important part of human life, and the development of veterinary drugs (VDs) has greatly impacted human health. Owing to increased affordability of and demand for drug development, VD manufacturing companies should have more PBPK models required to reduce drug production costs. So far, little attention has been paid on applying PBPK models for the development of VDs. This review begins with the development processes of VDs; then summarizes case studies of PBPK models in human or VD development; and analyzes the application, potential, and advantages of PBPK in VD development, including candidate screening, formulation optimization, food effects, target-species safety, and dosing optimization. Then, the challenges of applying the PBPK model to VD development are discussed. Finally, future opportunities of PBPK models in designing dosing regimens for intracellular pathogenic infections and for efficient oral absorption of VDs are further forecasted. This review will be relevant to readers who are interested in using a PBPK model to develop new VDs., (© 2021 John Wiley & Sons Ltd.)

Enrofloxacin (ENR) granules were developed to prevent and control the infections caused by foodborne zoonotic intestinal pathogens in our previous studies. To promote the further development of ENR granules and standardize their usage in pigs, a physiologically based pharmacokinetic (PBPK) model of the ENR granule in pigs was built to determine the withdrawal time (WT) and evaluate the toxicity to pigs. Meanwhile, the population WT was determined by a Monte Carlo analysis to guarantee pork safety. The fitting results of the model showed that the tissue residual concentrations of ENR, ciprofloxacin, and ENR plus ciprofloxacin were all well predicted by the built PBPK model (R 2 > 0.82). When comparing with the EMA's WT1.4 software method, the final WT (6 d) of the ENR granules in the population of pigs was well predicted. Moreover, by combining the cytotoxicity concentration (225.9 µg/mL) of ENR against pig hepatocytes, the orally safe dosage range (≤130 mg/kg b.w.) of the ENR granules to pigs was calculated based on the validated PBPK model. The well-predicted WTs and a few uses in animals proved that the PBPK model is a potential tool for promoting the judicious use of antimicrobial agents and evaluating the toxicity of the veterinary antimicrobial products.

Zoonotic intestinal pathogens threaten human health and cause huge economic losses in farming. Enrofloxacin (ENR) shows high antibacterial activity against common intestinal bacteria. However, its poor palatability and low aqueous solubility limit the clinical application of ENR. To obtain an ENR oral preparation with good palatability and high solubility, a granule containing an amorphous ENR solid dispersion (ENR-SD) was prepared. Meanwhile, a PBPK model of ENR in pigs was built based on the physiological parameters of pigs and the chemical-specific parameters of ENR to simulate the pharmacokinetics (PK) of ENR-SD granules in the intestinal contents. According to the results of parameter sensitivity analysis (PSA) and the predicted PK parameters at different doses of the model, formulation strategies and potential dose regimens against common intestinal infections were provided. The DSC and XRD results showed that no specific interactions existed between the excipients and ENR during the compatibility tests, and ENR presented as an amorphous form in ENR-SD. Based on the similar PK performance of ENR-SD granules and the commercial ENR soluble powder suggesting continued enhancement of the solubility of ENR, a higher drug concentration in intestinal contents could not be obtained. Therefore, a 1:5 ratio of ENR and stearic acid possessing a saturated aqueous solubility of 1190 ± 7.71 µg/mL was selected. The predictive AUC 24h /MIC 90 ratios against Campylobacter jejuni , Salmonella , and Escherichia coli were 133, 266 and 8520 (>100), respectively, suggesting that satisfactory efficacy against common intestinal infections would be achieved at a dose of 10 mg/kg b.w. once daily. The PSA results indicated that the intestinal absorption rate constant (Ka) was negatively correlated with the C max of ENR in the intestine, suggesting that we could obtain higher intestinal C max using P-gp inducers to reduce Ka, thus obtaining a higher C max . Our studies suggested that the PBPK model is an excellent tool for formulation and dose design.

In order to solve the antibiotic resistance, the research on antibiotic substitutes has received an extensive attention. Many studies have shown that β-glucan and mannan from yeast cell wall have the potential to replace antibiotics for the prevention and treatment of animal diseases, thereby reducing the development and spread of antibiotic-resistant bacterial pathogens. β-Glucan and mannan had a variety of biological functions, including improving the intestinal environment, stimulating innate and acquired immunity, adsorbing mycotoxins, enhancing antioxidant capacity, and so on. The biological activities of β-glucan and mannan can be improved by chemically modifying its primary structure or reducing molecular weight. In this paper, the structure, preparation, modification, and biological activities of β-glucan and mannan were reviewed, which provided future perspectives of β-glucan and mannan., Competing Interests: Declaration of competing interest Authors are not affiliated with or involved in any organization that has a direct or indirect economic interest in the subject discussed in the article. This article has not been submitted to, nor is under review at, another journal or other publishing location., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Staphylococcus aureus (S. aureus) is one of the most important zoonotic bacterial pathogens, infecting human beings and a wide range of animals, in particular, dairy cattle. Globally. S. aureus causing bovine mastitis is one of the biggest problems and an economic burden facing the dairy industry with a strong negative impact on animal welfare, productivity, and food safety. Furthermore, its smart pathogenesis, including facultative intracellular parasitism, increasingly serious antimicrobial resistance, and biofilm formation, make it challenging to be treated by conventional therapy. Therefore, the development of nanoparticles, especially liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanogels, and inorganic nanoparticles, are gaining traction and excellent tools for overcoming the therapeutic difficulty accompanied by S. aureus mastitis. Therefore, in this review, the current progress and challenges of nanoparticles in enhancing the S. aureus mastitis therapy are focused stepwise. Firstly, the S. aureus treatment difficulties by the antimicrobial drugs are analyzed. Secondly, the advantages of nanoparticles in the treatment of S. aureus mastitis, including improving the penetration and accumulation of their payload drugs intracellular, decreasing the antimicrobial resistance, and preventing the biofilm formation, are also summarized. Thirdly, the progression of different types from the nanoparticles for controlling the S. aureus mastitis are provided. Finally, the difficulties that need to be solved, and future prospects of nanoparticles for S. aureus mastitis treatment are highlighted. This review will provide the readers with enough information about the challenges of the nanosystem to help them to design and fabricate more efficient nanoformulations against S. aureus infections.

Due to the poor solubility and permeability of rifaximin (RFX), it is not effective against intracellular pathogens although it shows strong activity against most bacteria. To develop an effective mucoadhesive drug delivery system with a targeted release in bacterial infection site, RFX-loaded chitosan (CS)/carboxymethyl-chitosan (CMCS) nanogel was designed and systematically evaluated. FTIR, DSC, and XRD demonstrated that the nanogel was formed by interactions between the positively charged NH 3 + on CS and CMCS, and the negatively charged COO on CMCS. RFX was encapsulated into the optimized nanogel in amorphous form. The nanogel was a uniform spherical shape with a mean diameter of 171.07 nm. It had excellent sustained release, strong mucin binding ability, and pH-responsive properties of quicker swelling and release at acidic pH. It showed low hemolytic ratio and high antioxidant activity. The present investigation indicated that the CS-nanogel could be potentially used as a promising bacterial responsiveness drug delivery system., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (T max ) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the T max was shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.

Trueperella pyogenes is a major pathogenic organism of bovine uterus causing devastating economic losses. Clinical isolates of T. pyogenes demonstrated severe infection with high rate of disease progression than other pathogenic bacteria of uterus. We aimed to investigate the effectiveness of aditoprim, a novel dihydrofolate reductase inhibitor, based upon the ex-vivo pharmacodynamic analysis by using uterine fluid of cattle. In-vivo pharmacokinetic parameters were measured by high performance liquid choromatography and analyzed by winonline software (version 5.2.1). In-vitro minimum inhibitory concentration, mutant prevention concentration and time kill curves were determined with clinical isolates of Trueperell pyogenes. Our data showed that peak concentration (C max ) and area under the concentration time curve (AUC) were 6551.43 ± 1296.13 and 23585.22 ± 5126.47 μg/mL, respectively. Aditoprim showed potent antimicrobial activity against T. pyogenes (MIC = 0.25 μg/mL) and exhibited the concentration dependent antibacterial effect and produced in-vitro post antibiotic effect which was less than 1 h and increased with concentration. Pharmacodynamics values were modeled with pharmacokinetics parameters (PK/PD modeling) to simulate the efficacy of aditoprim for different dosage regimens. It was concluded that a dose of 2 mg/kg every 12h was expected to reach a bactericidal activity against T. pyogenes in endometritis., Competing Interests: Declaration of competing interest There is no conflict of interest between authors. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)