通讯机构：
[Zhao-Ying Liu] C;College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China<&wdkj&>Author to whom correspondence should be addressed.
摘要：
Gelsemium is a medicinal plant that has been used to treat various diseases, but it is also well-known for its high toxicity. Complex alkaloids are considered the main poisonous components in Gelsemium. However, the toxic mechanism of Gelsemium remains ambiguous. In this work, network pharmacology and experimental verification were combined to systematically explore the specific mechanism of Gelsemium toxicity. The alkaloid compounds and candidate targets of Gelsemium, as well as related targets of excitotoxicity, were collected from public databases. The crucial targets were determined by constructing a protein-protein interaction (PPI) network. Subsequently, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the bioprocesses and signaling pathways involved in the excitotoxicity corresponding to alkaloids in Gelsemium. Then, the binding affinity between the main poisonous alkaloids and key targets was verified by molecular docking. Finally, animal experiments were conducted to further evaluate the potential mechanisms of Gelsemium toxicity. A total of 85 alkaloids in Gelsemium associated with 214 excitotoxicity-related targets were predicted by network pharmacology. Functional analysis showed that the toxicity of Gelsemium was mainly related to the protein phosphorylation reaction and plasma membrane function. There were also 164 pathways involved in the toxic mechanism, such as the calcium signaling pathway and MAPK signaling pathway. Molecular docking showed that alkaloids have high affinity with core targets, including MAPK3, SRC, MAPK1, NMDAR(2B) and NMDAR(2A). In addition, the difference of binding affinity may be the basis of toxicity differences among different alkaloids. Humantenirine showed significant sex differences, and the LD50 values of female and male mice were 0.071 mg center dot kg(-1) and 0.149 mg center dot kg(-1), respectively. Furthermore, we found that N-methyl-D-aspartic acid (NMDA), a specific NMDA receptor agonist, could significantly increase the survival rate of acute humantenirine-poisoned mice. The results also show that humantenirine could upregulate the phosphorylation level of MAPK3/1 and decrease ATP content and mitochondrial membrane potential in hippocampal tissue, while NMDA could rescue humantenirine-induced excitotoxicity by restoring the function of mitochondria. This study revealed the toxic components and potential toxic mechanism of Gelsemium. These findings provide a theoretical basis for further study of the toxic mechanism of Gelsemium and potential therapeutic strategies for Gelsemium poisoning.
作者：
Ji, Chunxiao;Feng, Jia;Li, Siying;Yang, Hui;Wang, Hui;...
期刊：
Viruses,2023年15(1):138- ISSN：1999-4915
通讯作者：
Tao Zhang<&wdkj&>Yu He<&wdkj&>Wei Liu
作者机构：
[Liu, Wei; Ji, Chunxiao] Hunan Agr Univ, Coll Vet Med, Changsha 410128, Peoples R China.;[Wang, Hui; Wang, Hongliang; Geng, Xiangchang; He, Yu; Liu, Zengzai; Feng, Jia; Yang, Hui; Zhang, Tao] Changsha Anim Dis Control Ctr, Changsha 410013, Peoples R China.;[Li, Siying] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Peoples R China.
通讯机构：
[Tao Zhang; Yu He; Wei Liu] A;Authors to whom correspondence should be addressed.<&wdkj&>Changsha Animal and Plant Disease Control Center, Changsha 410000, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China
摘要：
The objective of this study was to examine longitudinal trends in the prevalence of dogs that are successfully immunized against rabies virus (as measured by sufficient serum antibodies) in Changsha, an urban center of China. The secondary objective was to investigate the factors affecting the seroprevalence of rabies virus antibodies in dogs. In this study, 4515 canine serum samples were collected from 57 pet hospitals (immunization points) during the period of 2015–2021 in five major urban areas of Kaifu, Furong, Tianxin, Yuhua, and Yuelu in Changsha, China. The enzyme-linked immunosorbent assay (ELISA) method was used to analyze the level and trend of rabies virus antibodies in serum and further evaluate the potential factors affecting the immunization effect from five factors: sex, age, time interval after most recent vaccination and sample collection, number of vaccinations, and vaccine manufacturer. The results showed that the seroconversion from the urban dog in Changsha steadily increased from 46.13% to 73.38% during 2015–2017. The seropositivity prevalence remained above the international standard (70%) from 2018 to 2020 and up to 90.99% in 2021. Further analysis showed that the seroconversion of rabies virus among dogs was significantly affected by the age, the number of vaccinations, time interval after the most recent vaccination and sample collection, and vaccine manufacturer, while sex had less influence. The overall rabies vaccination situation in urban areas of Changsha generally meets international standards, with only a few areas showing low levels of antibodies in dogs after vaccination and risk of infectiousness. Therefore, it is recommended that the first vaccination should be given when the dog is about three months old and regularly repeated every year after that. At the same time, antibody concentrations in dogs, especially in newborn puppies and older dogs, need to be tested promptly after vaccination at the required time to ensure that they are at a high level of immune protection, which can strengthen the supervision of rabies.
期刊：
JOURNAL OF ORGANIC CHEMISTRY,2023年88(17):12311-12318 ISSN：0022-3263
通讯作者：
Gui, QW;Yin, YL
作者机构：
[Liu, Xiaoying; Zhu, Mengxue; Gui, Qing-Wen; Cai, Tian-cheng; Xia, Jingjing; Liu, Yuxuan; Gui, QW] Hunan Agr Univ, Coll Chem & Mat Sci, Changsha 410128, Peoples R China.;[Xie, Junyan; Yin, YL; Yin, Yulong] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Ctr Technol Innovat Synthet Biol, Tianjin 300308, Peoples R China.;[Wen, Lixin] Hunan Agr Univ, Coll Vet Med, Changsha 410128, Hunan, Peoples R China.
通讯机构：
[Yin, YL ] C;[Gui, QW ] H;Hunan Agr Univ, Coll Chem & Mat Sci, Changsha 410128, Peoples R China.;Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Ctr Technol Innovat Synthet Biol, Tianjin 300308, Peoples R China.
摘要：
Dithiocarbamates synthesis is extremely important in plenty of biomedical and agrochemical applications, especially fungicide development, but remains a great challenge. In this work, we have successfully developed a multicomponent reaction protocol to convert H(2)S into S-alkyl dithiocarbamates under constant current conditions. No additional oxidants nor additional catalysts are required, and due to mild conditions, the reactions display a broad substrate scope, including varieties of thiols or disulfides.
摘要：
Subacute mycotoxin exposure in food is commonly overlooked. As one of the most toxic trichothecene mycotoxins, the T-2 toxin severely pollutes human foods and animal feeds. In our study, we investigated the effects of low-dose T-2 toxin on glucose and lipid metabolic function and further investigated the protective effect of tannic acid (TA) in C57BL/6J mice. Results showed that low-dose T-2 toxin significantly impaired blood glucose and lipid homeostasis, promoted ferroptosis in the pancreas and subsequent repression of insulin secretion in β-cells, and impacted hepatic glucose and lipid metabolism by targeted inhibition of the insulin receptor substrate (IRS)/phosphatidylin-ositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which induced insulin resistance and steatosis in the liver. TA treatment attenuated pancreatic function and hepatic metabolism by ameliorating oxidative stress and insulin resistance in mice. These findings provide new perspectives on the toxic mechanism and intervention of chronic subacute toxicity of foodborne mycotoxins.
作者机构：
[Liu, YS; Zeng, Jianguo; Liu, Yisong; Xiao, Gang; Cheng, Pi; Yang, Yang] Hunan Agr Univ, Coll Vet Med, Changsha 410125, Peoples R China.;[Liu, YS; Zeng, Jianguo; Liu, Yisong; Cheng, Pi; Yang, Yang] Chinese Vet Med, Hunan Key Lab, Changsha 410125, Peoples R China.
通讯机构：
[Liu, YS ; Zeng, JG] H;Hunan Agr Univ, Coll Vet Med, Changsha 410125, Peoples R China.;Chinese Vet Med, Hunan Key Lab, Changsha 410125, Peoples R China.
关键词：
intestinal inflammation;cellular signaling pathway;Chinese herbal compounds;Chinese herbal formulae;gut health
摘要：
Intestinal inflammation is a chronic gastrointestinal disorder with uncertain pathophysiology and causation that has significantly impacted both the physical and mental health of both people and animals. An increasing body of research has demonstrated the critical role of cellular signaling pathways in initiating and managing intestinal inflammation. This review focuses on the interactions of three cellular signaling pathways (TLR4/NF-kappa B, PI3K-AKT, MAPKs) with immunity and gut microbiota to explain the possible pathogenesis of intestinal inflammation. Traditional medicinal drugs frequently have drawbacks and negative side effects. This paper also summarizes the pharmacological mechanism and application of Chinese herbal compounds (Berberine, Sanguinarine, Astragalus polysaccharide, Curcumin, and Cannabinoids) and formulae (Wumei Wan, Gegen-Qinlian decoction, Banxia xiexin decoction) against intestinal inflammation. We show that the herbal compounds and formulae may influence the interactions among cell signaling pathways, immune function, and gut microbiota in humans and animals, exerting their immunomodulatory capacity and anti-inflammatory and antimicrobial effects. This demonstrates their strong potential to improve gut inflammation. We aim to promote herbal medicine and apply it to multispecies animals to achieve better health.
作者机构：
[Lin, Yuan; Zhang, Taojie; Wang, Changjian; Hu, Qiaoyun; Zhang, Kun; Peng, Zhi; Zhai, Wang; Zhang, Pengxuan; Tang, Xiaomin; He, Shicheng] Hunan Prov Ctr Anim Dis Control & Prevent, Changsha 410128, Peoples R China.;[Zhai, Wang; Zhang, Pengxuan] Hunan Agr Univ, Coll Vet Med, Changsha 410128, Peoples R China.;[Yu, Siyu] Technol Ctr Changsha Customs, Changsha 410128, Peoples R China.;[Ge, Shenghu] Hebei Mingzhu Biotechnol Co Ltd, Xingtai 055700, Peoples R China.
通讯机构：
[Changjian Wang] H;Hunan Provincial Center for Animal Disease Control and Prevention, Changsha 410128, China<&wdkj&>Author to whom correspondence should be addressed.
关键词：
porcine reproductive and respiratory syndrome virus;epidemiology;genetic characteristics;ORF5 gene;China
摘要：
Simple Summary Porcine reproductive and respiratory syndrome virus (PRRSV) is the major cause of huge economic losses to the pig industry in China. The present study was performed to investigate the epidemiological characteristics of PRRSV in two provinces (Hunan and Hebei) in China in 2021. The results revealed the high prevalence of PRRSV in the healthy and diseased pigs in Hunan and Hebei province. The PRRSV lineages prevalent in Hunan and Hebei province were diverse, while the NADC30-like (sublineage 1.8) and HP-PRRSV (sublineage 8.7) strains predominated. Moreover, four PRRSV strains were isolated in this study, and a novel sublineage 1.8 strain recombinant from the NADC30-like strain and JXA1 (or MLV)-like strain was confirmed via investigating its complete genomic characteristics. In summary, this study has offered the latest information on the epidemiology and genetic characteristics of PRRSV in Hunan and Hebei province, which would be beneficial for PRRS control in the future. Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant threat to the pig industry in China. However, the epidemiological characteristics of PRRSV after the outbreak of African swine fever in China were not thoroughly investigated. In the present study, the serological and epidemiological investigations of PRRSV in pigs from the Hunan and Hebei provinces of China were assessed. The results showed that 73.12% (95% CI 71.74-74.49) of pigs were positive for PRRSV-special antibody by enzyme-linked immunosorbent assay. Out of 5799 samples, 482 (8.31%, 95% CI 7.60-9.02) samples were positive for PRRSV nucleic acids. The positive rates of PRRSV in healthy pigs from farms and slaughterhouses were 2.27% (47/2072) and 7.70% (217/2818), which were lower than that in diseased pigs (23.98%, 218/909). Furthermore, the full-length OFR5 gene sequences of 43 PRRSV strains were sequenced and analysed. Phylogenetic analysis revealed that 43 isolates were classified into three lineages, namely lineage 1 (n = 24), lineage 8 (n = 15), and lineage 3 (n = 4). Lineage 1 could be further divided into sublineage 1.5 (n = 2) and sublineage 1.8 (n = 22), and lineage 8 was classified into sublineage 8.1 (n = 3) and sublineage 8.7 (n = 12). Collectively, our findings revealed the severe prevalence of PRRSV in the Hunan and Hebei provinces, where sublineage 1.8 and sublineage 8.7 predominated. The present study provides the update information of the epidemiological and genetic characteristics of PRRSV in the investigated regions, which will be beneficial for PRRS control.
摘要：
ScopeOlive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared.Methods and resultsNinety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids.ConclusionOlive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver. Olive oil, rapeseed oil, and lard are dietary fats that are rich in monounsaturated fatty acids. This study investigates the effects of three dietary oils on hepatic glucose and lipid metabolism in mice. Compared to rapeseed oil and lard, olive oil is most likely to cause hepatic lipid deposition by activating the metabolic pathways of starch and sucrose. image
摘要：
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata (Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.
通讯机构：
[Nengshui Ding] S;[Ruiming Hu] D;State Key Laboratory for Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang, China<&wdkj&>Key Laboratory of Swine Nutrition and Feed Science of Fujian Province, Aonong Group, Zhangzhou, China<&wdkj&>Department of Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China;No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, China<&wdkj&>Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, China
摘要：
Porcine Teschovirus (PTV), also named Teschovirus A, is prevalent in pig populations, mainly causing neurological symptoms, diarrhea, pneumonia, and reproductive failure, however the morbidity and mortality are usually low in pig farms. In this study, we reported a PTV outbreak investigation in one large-scale pig farm in China with severe symptoms including diarrhea, lethargy, locomotor ataxia, nystagmus, paralysis of the hind limbs, and coma in piglets. More importantly, the mortality reached 38% in suckling pigs, which is remarkably high in PTV history. A novel PTV strain, named HeNZ1, was isolated from cerebral samples of one suckling pig and the genome sequence was obtained by NGS sequencing. Phylogenetic and evolutionary divergence analyses revealed that HeNZ1 belongs to PTV genotype 2. Surprisingly, the VP1 coding region of HeNZ1 shares the highest sequence similarity with European PTV-2 strains, instead of China domestic PTV-2 strains, implying it may not derive from China local PTV-2 strains. Multiple sequence alignment and B cell epitope prediction of PTV VP1 and VP2 protein revealed 10 B cell epitopes, 5 mutant clusters and 36 unique mutation sites, of which 19 unique mutation sites are located in B cell epitopes and exposed on the surface of VP1 or VP2, implying significant antigenic drift potential of HeNZ1. These results indicate that HeNZ1 is a highly virulent PTV-2 strain, which capable of causing severe neurological symptoms and high mortality in piglets. Bioinformatic analysis suggest that HeNZ1 is genetically and antigenically different from other Chinese PTV-2 strains. Overall, current case expanded our understanding of PTV-2 clinical spectrum and revealed the emergence of a highly virulent PTV-2 strain with substantial genetic diversity and antigenic drift potential in VP1 and VP2.
摘要：
Gelsemium elegans (G.elegans) is a plant of the Loganiaceae family, known for its indole alkaloids, including gelsemine, koumine, and gelsenicine. Gelsemine and koumine are well-studied active alkaloids with low toxicity, valued for their anti-anxiety and analgesic properties. However, gelsenicine, another important alkaloid, remains underexplored due to its high toxicity. This study focuses on evaluating the analgesic properties of gelsenicine and comparing them with gelsemine and koumine. The results indicate that all three alkaloids exhibit robust analgesic properties, with gelsemine, koumine, and gelsenicine showing ED50 values of 0.82 mg/kg, 0.60 mg/kg, and 8.43 mu g/kg, respectively, as assessed by the hot plate method. Notably, the therapeutic dose of gelsenicine was significantly lower than its toxic dose (LD50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyR alpha 3 and Gephyrin. The PGE2 model group showed decreased expression levels of GlyR alpha 3 and Gephyrin, while groups treated with gelsemine, koumine, and gelsenicine were able to reverse this decrease. These results suggest that gelsenicine effectively alleviates PGE2-induced hyperalgesia by upregulating the expression of GlyR alpha 3 and Gephyrin, which are key targets of the Gly receptor pathway.
