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Infection by multidrug-resistant avian pathogenic Escherichia coli (APEC) in chickens always leads to the uselessness of antibiotics, highlighting the need for alternative antibacterial agents. Sophora flavescens and Coptis chinensis have been a classical combination used together in Traditional Chinese Medicine (TCM) formulas to treat diseases with similar symptoms to colibacillosis for an extended period, but the effect of their active ingredients' combination on APEC infection remains unstudied. The objective of this study was to explore the synergistic effect of matrine and berberine hydrochloride on colibacillosis caused by an isolated multidrug-resistant APEC. In this study, a highly pathogenic E. coli was isolated from the liver of a diseased chicken in a farm suspected of colibacillosis, and it was resistant to multiple antibiotics. The LD50 of the strain was approximately 3.759×108 CFU/mL. The strain harbored several antibiotic resistance genes and virulence genes. Matrine and berberine hydrochloride have synergistic antibacterial effect against the isolated strain in vitro. The combined use of matrine and berberine hydrochloride exhibited synergistic effects in the treatment of APEC infection by regulating the organ indices, improving the pathological situation, decreasing the bacterial load, and regulating the inflammatory factors to enhance the survival rate of chickens in vivo. These results provided a foundation for revealing the effective effects and possible mechanisms of matrine and berberine hydrochloride as potential antimicrobial agents on diseases caused by multidrug-resistant APEC in chickens.
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In recent years, the evolution of antibiotic resistance has led to the inefficacy of several antibiotics, and the reverse of resistance was a novel method to solve this problem. We previously demonstrated that matrine (Mat) and berberine hydrochloride (Ber) had a synergistic effect against multidrug-resistant Escherichia coli (MDREC). This study aimed to demonstrate the effect of Mat combined with Ber in reversing the resistance of MDREC. The MDREC was sequenced passaged in the presence of Mat, Ber, and a combination of Mat and Ber, which did not affect its growth. The reverse rate was up to 39.67% after MDREC exposed to Mat + Ber for 15 days. The strain that reversed resistance was named drug resistance reversed E. coli (DRREC) and its resistance to ampicillin, streptomycin, gentamicin, and tetracycline was reversed. The MIC of Gentamicin Sulfate (GS) against DRREC decreased 128-fold to 0.63 µg/mL, and it was stable within 20 generations. Furthermore, the susceptible phenotype of DRREC remained stable within 20 generations, as well. The LD50 of DRREC for chickens was 8.69 × 109 CFU/mL. qRT-PCR assays revealed that the transcript levels of antibiotic-resistant genes and virulence genes in the DRREC strain were significantly lower than that in the MDREC strain (P < 0.05). In addition, GS decreased the death, decreased the bacterial loading in organs, alleviated the injury of the spleen and liver, and decreased the cytokine levels in the chickens infected by the DRREC strain. In contrast, the therapeutic effect of GS in chickens infected with MDREC was not as evident. These findings suggest that the combination of Mat and Ber has potential for reversing resistance to MDREC.
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Alcaloides , Antibacterianos , Berberina , Pollos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli , Escherichia coli , Gentamicinas , Matrinas , Pruebas de Sensibilidad Microbiana , Enfermedades de las Aves de Corral , Quinolizinas , Animales , Gentamicinas/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Berberina/farmacología , Antibacterianos/farmacología , Quinolizinas/farmacología , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Alcaloides/farmacología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Virulencia/efectos de los fármacos , Sinergismo FarmacológicoRESUMEN
Duck hepatitis A virus 1 (DHAV-1) is the primary cause of duck viral hepatitis, leading to sudden mortality in ducklings and significant economic losses in the duck industry. However, little is known about how DHAV-1 affects duckling liver at the molecular level. We conducted an analysis comparing the expression patterns of mRNAs and miRNAs in DHAV-1-infected duckling livers to understand the underlying mechanisms and dynamic changes. We identified 6,818 differentially expressed mRNAs (DEGs) and 144 differentially expressed microRNAs (DEMs) during DHAV-1 infection. Functional enrichment analysis of DEGs and miRNA target genes using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed their potential involvement in innate antiviral immunity, mitophagy, and pyroptosis. We constructed coexpression networks of mRNA-miRNA interactions and confirmed key DEMs (novel-mir333, novel-mir288, novel-mir197, and novel-mir71) using RT-qPCR. Further investigation demonstrated that DHAV-1 activates the RLRs signaling pathway, disrupts mitophagy, and induces pyroptosis. In conclusion, DHAV-1-induced antiviral immunity is closely linked to mitophagy, suggesting it could be a promising therapeutic target.
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Patos , Virus de la Hepatitis del Pato , Hepatitis Viral Animal , MicroARNs , Mitofagia , Enfermedades de las Aves de Corral , ARN Mensajero , Transducción de Señal , Animales , Patos/genética , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/inmunología , Virus de la Hepatitis del Pato/fisiología , Hepatitis Viral Animal/virología , Hepatitis Viral Animal/genética , Hepatitis Viral Animal/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Infecciones por Picornaviridae/veterinaria , Infecciones por Picornaviridae/virología , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/genética , Transcriptoma , Inmunidad Innata/genéticaRESUMEN
Background: Traditional Chinese medicine (TCM) is widely used in humans and animals, which is very important for health. TCM affects the body 's immunity and changes in intestinal flora. This study was conducted to investigate the effects of dietary Hong-bailanshen (HBLS) supplementation in horses on serum biochemical profile, antioxidant enzymes and gut microbiota. Methods: In this study, five horses were selected. On day 0, 14, 28, blood samples and feces were collected on days 0, 14, and 28 to analyse gut microbiota, serum biochemical and redox indexes. Results: The results showed that the addition of HBLS to horse diets significantly decreased the level of alanine aminotransferase, alkaline phosphatase, creatine kinase and malondialdehyde (p < 0.05, p < 0.01) and significantly increased the activity of total antioxidant capacity, superoxide dismutase and catalase (p < 0.05, p < 0.01). Compared with day 14, the levels of alanine aminotransferase, alkaline phosphatase and creatine kinase were significantly decreased; however, the level of catalase was significantly increased in the horses continuously fed with HBLS for 28 days (p < 0.05, p < 0.01). Alpha diversity analysis was performed that chao1 (p < 0.05), observed_specicies, faith'pd and goods_coverage upregulated in the horses fed HBLS. A total of 24 differential genera were detected adding HBLS to diet increased the abundance of Bacillus, Lactobacillaceae, Leuconostocaceae, Christensenellaceae, Peptostreptococcaceae, Faecalibacterium, Erysipelotrichaceae, Pyramidobacter, Sphaerochaeta, WCHB1-25, Bacteria, Oscillospira, and Acetobacteraceae, while reduced Aerococcus, EtOH8, Syntrophomonas, Caulobacter, Bradyrhizobiaceae, W22, Succinivibrionaceae, and Desulfovibrio (p < 0.05, p < 0.01). Conclusion: Adding HBLS to the diet could be a potentially effective strategy to improve horses' health.
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In pet clinics, the number of cases using trauma drugs accounts for >10% of the total number of cases, and most wounds are healing by second intention. The prolongation of wound healing time causes inconvenience and burden to pets and pet owners. Therefore, how to reduce wound healing time and achieve maximum recovery of tissue function and aesthetics is one of the focuses of veterinary clinical practice. Wound suppuration caused by Staphylococcus aureus and Pseudomonas aeruginosa is the main cause of delaying wound healing. Clinically, available antimicrobial treatments are almost exhausted due to the production of large numbers of resistant bacteria. At present, there are no bacteria resistant to traditional Chinese medicine (TCM), which makes TCM have the potential to become an effective drug for the treatment of bacterial infections, so the use of TCM in the treatment of traumatic infections has broad prospects. Based on the characteristics of infection syndrome, three different prescriptions were formulated in our laboratory, and the most effective prescription and dosage form was screened and named Lianrong Healing Cream (LRHC). The results showed that LRHC regulated the expression of fibroblast growth factor-2 (FGF-2), epidermal growth factor-1 (EGF-1), transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor-1 (VEGF-1) genes in wound tissues and fibroblasts, thereby accelerating wound healing and repairing wound appearance and function. The results of this study may be help to develop TCM formulation for traumatic infections.
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Medicina Tradicional China , Cicatrización de Heridas , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Crecimiento Epidérmico/farmacologíaRESUMEN
The modified rougan decoction (MRGD) compound formula has been proven a certain ability to relieve lipopolysaccharide-enrofloxacin (LPS-ENR)-induced liver oxidant injury in chickens. Recent advances have shown that mitochondrial dysfunction affects the development of many diseases, leading to increased interest in exploring its effects. Using LPS-ENR-injured in vivo and in vitro to further evaluate the effects of MRGD on mitochondrial structure and function, and emphasized further investigation of its molecular mechanism. After LPS-ENR treatment, the levels of inflammation and apoptosis markers were increased, along with higher mitochondrial injury. Results showed that MRGD reduced inflammatory factors expression and inhibited the nuclear translocation of NF-κB P65, reducing the inflammatory response in vivo and in vitro. Additionally, MRGD pretreatment inhibited mitochondrial dysfunction, mitochondrial oxidative stress, and mitochondrial pathway apoptosis by maintaining mitochondrial structure and function. Moreover, treatment with the inhibitor EX527 showed that MRGD promoted mitochondrial biogenesis ability through the SIRT1/PGC-1α pathway and interfered with mitochondrial dynamics, and activate Nrf2. In summary, MRGD played a key role in promoting mitochondrial function and thus alleviating hepatocyte apoptosis in vivo and in vitro at least in part.
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Lipopolisacáridos , Sirtuina 1 , Animales , Sirtuina 1/genética , Sirtuina 1/metabolismo , Lipopolisacáridos/farmacología , Pollos/metabolismo , Mitocondrias/metabolismo , Apoptosis , Transducción de Señal , Hepatocitos/metabolismo , Estrés OxidativoRESUMEN
In order to ascertain the mechanism underlying the therapeutic efficacy of Bush sophora root polysaccharides (BSRPS) and phosphorylated Bush sophora root polysaccharides (pBSRPS) in the treatment of in duck viral hepatitis (DVH), an investigation was conducted to assess the protective impact of BSRPS and pBSRPS against duck hepatitis A virus type 1 (DHAV-1) induced mitochondrial dysfunction both in vivo and vitro. The BSRPS underwent modification through the utilization of the sodium trimetaphosphate - sodium tripolyphosphate method, and was subsequently characterized though Fourier infrared spectroscopy and scanning electron microscopy. Following this, the degree of mitochondrial oxidative damage and dysfunction was described through the use of fluorescence probes and various antioxidative enzyme assay kits. Furthermore, the utilization of transmission electron microscopy facilitated the observation of alterations in the mitochondrial ultrastructure within the liver tissue. Our findings demonstrated that both BSRPS and pBSRPS effectively mitigated mitochondrial oxidative stress and conserved mitochondrial functionality, as evidenced by heightened antioxidant enzyme activity, augmented ATP production, and stabilized mitochondrial membrane potential. Meanwhile, the histological and biochemical examinations revealed that the administration of BSRPS and pBSRPS resulted in a reduction of focal necrosis and infiltration of inflammatory cells, thereby mitigating liver injury. Additionally, both BSRPS and pBSRPS exhibited the ability to maintain liver mitochondrial membrane integrity and enhance the survival rate of ducklings infected with DHAV-1. Notably, pBSRPS demonstrated superior performance in all aspects of mitochondrial function compared to BSRPS. The findings indicated that maintaining mitochondrial homeostasis is a crucial factor in DHAV-1 infections, and the administration of BSRPS and pBSRPS may mitigate mitochondrial dysfunction and safeguard liver function.
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Virus de la Hepatitis del Pato , Hepatitis Viral Animal , Hepatitis Viral Humana , Infecciones por Picornaviridae , Enfermedades de las Aves de Corral , Sophora , Animales , Hepatitis Viral Animal/tratamiento farmacológico , Hepatitis Viral Animal/patología , Patos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Sophora/química , Mitocondrias , Polisacáridos/química , Hepatitis Viral Humana/tratamiento farmacológico , Infecciones por Picornaviridae/tratamiento farmacológico , Infecciones por Picornaviridae/patología , Enfermedades de las Aves de Corral/tratamiento farmacológicoRESUMEN
Escherichia coli is one of the most common pathogenic bacteria in diarrheal chickens, leading to serious economic losses in the poultry industry. The limited effect of antibiotics on antibiotic-resistant E. coli makes this bacterium a potential threat to human health. Yujin powder (YJP) has been reported as an agent that releases the symptoms caused by E. coli for a long time. The objective of this study is to investigate the effect of Yujin powder (YJP) and its components, Scutellariae Radix (SR) and Baicalin (Bac), anti-against multi-drug-resistant E. coli in vitro and in vivo. A multi-drug-resistant bacteria was isolated and identified from a clinical diarrheal chick. Then, the anti-bacterial effects of drugs were assessed in vitro and in vivo by analyzing the bacteria loads of organs, the levels of endotoxin, TNF-α, IL-1ß, and IL-6 of the serum. Results found that the pathogenic E. coli was resistant to 19 tested antibiotics. YJP, SR, and Bac could directly inhibit the growth of this strain at high concentrations in vitro, and presents obvious anti-bacterial effects by reducing the bacterial loads, the release of endotoxin, and inflammation in vivo, which was much more effective than the resistant antibiotic ciprofloxacin. This study demonstrates that those natural medicines have the potential to be used as novel treatments to treat the disease caused by this isolated MDREC strain.
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Liver injury plays a heavy burden on the chicken industry. Although modified rougan decoction is a prescription for the treatment of liver disease based on the classical prescription of rougan decoction (containing peony and licorice). However, the effect and mechanism of modified rougan decoction on the liver remain unclear. In this study, the effects of the water extracts (MRGD) and the alcohol precipitates of water extracts (MRGDE) against lipopolysaccharide-enrofloxacin (LPS-ENR)-induced hepatotoxicity were discussed in vivo and in vitro. The isolated hepatocytes and 128 one-day-old Hyline chickens were considered research objects. The indices of liver injury and oxidative stress were evaluated by hematoxylin and eosin (H&E) stained and the assay kits, and the nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway was detected by the RT-PCR, western blot, and immunofluorescence tests. All data were analyzed using the IBM SPSS 20.0 software. In vivo, the structural integrity of the liver was maintained, AST, ALT, and MDA levels were decreased, and antioxidant enzymes were increased, confirming that the oxidative stress was reduced and liver injury was alleviated. Correspondingly, MRGD and MRGDE were observed to improve cell viability and decrease lactate dehydrogenase (LDH) in vitro, and the cell oxidative damage was reduced. In addition, the nuclear translocation of Nrf2 was improved significantly, and the mRNA and protein expression levels of the related genes were upregulated. In conclusion, MRGD and MRGDE can exert a protective effect against LPS-ENR-induced hepatotoxicity by activating the Nrf2/ARE pathway, which might be a potential therapeutic prescription for preventing or treating liver injury. Notably, no significant difference was found between the 2 extracts, suggesting that a depth extraction method did not always improve the efficacy of natural medicine. Our results provided new insights into finding effective hepatoprotective medicine.
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Antioxidantes , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Antioxidantes/metabolismo , Lipopolisacáridos/toxicidad , Pollos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Enrofloxacina/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/veterinaria , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Estrés Oxidativo , Hígado/metabolismoRESUMEN
Staphylococcus saprophyticus is frequently involved in various difficult-to-treat infections due to the formation of biofilms. To identify useful antibiofilm strategies, this study explored the efficacy and mechanism of baicalin in enhancing the ability of azithromycin against multidrug-resistant Staphylococcus saprophyticus-Liu-2016-Liyang, China-francolin (MDRSS) biofilms in vitro and in vivo. When azithromycin was used in combination with baicalin, the minimum inhibitory concentration in biofilm (MICB) for azithromycin decreased 4- to 512-fold. Compared with the azithromycin and baicalin groups, the combination of azithromycin and baicalin could not reduce the biofilm biomass, but the dispersion rates of biofilm were decreased and the bactericidal ability was increased. Furthermore, the relative transcript levels of WalK/R system-related genes were upregulated by the addition of baicalin or azithromycin plus baicalin compared with that of the azithromycin and blank control groups. The strong correlation relationship between the WalK/R system and the bactericidal index demonstrated that baicalin enhanced the bactericidal effect of azithromycin on MDRSS biofilms by modulating the WalK/R system. In the mouse cutaneous infection model, the combination of azithromycin and baicalin succeeded in eradicating MDRSS and decreasing pathological injuries. This study indicated that baicalin has the potential to be an adjuvant to enhance the antimicrobial activity of azithromycin against MDRSS in the biofilm form by modulating the WalK/R system.
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Azitromicina , Staphylococcus aureus Resistente a Meticilina , Animales , Antibacterianos/farmacología , Azitromicina/farmacología , Biopelículas , Ratones , Pruebas de Sensibilidad Microbiana/veterinaria , Staphylococcus saprophyticusRESUMEN
In recent years, the efficacy of antibiotics has been threatened by the evolution of bacterial resistance. We previously demonstrated that baicalin (Bac) showed synergies with azithromycin (Azm) against Azm-resistant Staphylococcus saprophyticus (ARSS). The aim of this study was to explore the roles of Bac in reversing the resistance of ARSS to Azm. The ARSS was sequentially passaged for 20 days with the sub-MIC (minimum inhibitory concentration) of Bac. The strain that recovered sensitivity to Azm was named Azm-sensitive S. saprophyticus (ASSS). The sub-MIC of Bac reversed the resistance of ARSS to Azm. The MIC of Azm against the ASSS strain was 0.488 mg/l, and it was stable within 20 passages. The highest rate of resistance reversal reached 3.09% after ARSS was exposed to 31.25 mg/l Bac for 20 days. Furthermore, semiquantitative biofilm and RT-PCR assays reflected that the ability of biofilm formation and the transcript levels of msrA, mphC, and virulence-associated genes in the ASSS strain were significantly lower than those of the ARSS strain (p < 0.05). Simultaneously, Azm delayed the start time of death, alleviated the injury of the kidney, and decreased the bacterial burden in organs and cytokine levels in mice infected with ASSS. In contrast, Azm did not have a good therapeutic effect on mice infected with ARSS. Therefore, Bac has the potential to be an agent that reversed the resistance of ARSS to Azm.
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Accumulating evidence indicated that oxidative stress is closely related to inflammation and the progression of multiple chronic diseases, which seriously threaten the host health. Currently, multiple plant-derived polysaccharides have been demonstrated to ameliorate the negative effects of oxidative stress on the host, but the potential protective effect of radix paeoniae alba polysaccharide (RPAP) on host have not been well characterized. Here, we investigated whether different doses of RPAP administration could alleviate lipopolysaccharide (LPS)-induced intestinal injury and gut microbial dysbiosis in mice. Results indicated that RPAP administration effectively alleviated LPS-induced intestinal damage in dose dependent. Additionally, amplicon sequencing showed that RPAP administration reversed the significant decrease in gut microbial diversity caused by LPS exposure and restored the alpha-diversity indices to normal levels. Microbial taxonomic investigation also indicated that LPS exposure resulted in significant changes in the gut microbial composition, characterized by a decrease in the abundances of beneficial bacteria (Lactobacillus, Alistipes, Bacillus, Rikenellaceae_RC9_gut_group, etc.) and an increase in the contents of pathogenic bacteria (Klebsiella, Helicobacter, Enterococcus, etc.). However, RPAP administration, especially in high doses, could improve the composition of the gut microbiota by altering the abundance of some bacteria. Taken together, this study demonstrated that RPAP administration could ameliorate LPS-induced intestinal injury by regulating gut microbiota. Meanwhile, this also provides the basis for the popularization and application of RPAP and alleviating oxidative stress from the perspective of gut microbiota.
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Hexavalent chromium [Cr (VI)] is a hazardous heavy metal that pollutes soil, water and crops. Moreover, its prolonged exposure can harm the gastrointestinal system, liver and respiratory tract in different species, but knowledge regarding Cr (VI) influence on gut microbiota in chickens remains scarce. Therefore, this study was performed to investigate the impact of Cr (VI) on gut microbiota in chickens. Results revealed that the gut microbiota in Cr (VI)-induced chickens exhibited a distinct reduction in alpha diversity, accompanied by significant shifts in microbial composition. Specifically, Firmicutes and Bacteroidetes were the most dominant phyla in the control chickens, whereas Firmicutes and Actinobacteria were observed to be predominant in the Cr (VI)-induced populations. Moreover, the types and relative abundances of predominant bacterial genus in control and Cr (VI)-induced chickens were also different. Bacterial taxonomic analysis revealed that the relative abundances of 3 phyla and 7 genera obviously increased, whereas 8 phyla and 30 genera dramatically decreased during Cr (VI) induction. Among them, 1 phylum (Deferribacteres) and 5 genera (Butyricicoccus, Butyricimonas, Intestinimonas, Lachnospiraceae_FCS020_group and Ruminococcaceae_V9D2013_group) even could not be found in the gut microbial community of Cr (VI)-induced chickens. Taken together, our study indicated that the long-term exposure to Cr (VI) dramatically alter the gut microbial diversity and composition in chickens. Notably, it represents a breakthrough in understanding the impact of Cr (VI) on the intestinal microbiota of chickens.