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Article ; Online: The gut microbiota contributes to the infection of bovine viral diarrhea virus in mice.

Zhang, Zecai / Huang, Jiang / Li, Chuang / Zhao, Zhicheng / Cui, Yueqi / Yuan, Xueying / Wang, Xue / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo

Journal of virology

2024 Volume 98, Issue 2, Page(s) e0203523

Abstract: Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and ... ...

Abstract	Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on
MeSH term(s)	Animals ; Cattle ; Mice ; Bovine Virus Diarrhea-Mucosal Disease/complications ; Bovine Virus Diarrhea-Mucosal Disease/microbiology ; Bovine Virus Diarrhea-Mucosal Disease/therapy ; Bovine Virus Diarrhea-Mucosal Disease/virology ; Butyrates/metabolism ; Caspase 3/metabolism ; Caspase 9/metabolism ; Diarrhea ; Diarrhea Viruses, Bovine Viral/pathogenicity ; Diarrhea Viruses, Bovine Viral/physiology ; Dysbiosis/complications ; Dysbiosis/microbiology ; Dysbiosis/virology ; Extracellular Signal-Regulated MAP Kinases/immunology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Disease Models, Animal
Chemical Substances	Butyrates ; Caspase 3 (EC 3.4.22.-) ; Caspase 9 (EC 3.4.22.-) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Interferon Type I ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.02035-23
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Article ; Online: Phlorizin Limits Bovine Viral Diarrhea Virus Infection in Mice via Regulating Gut Microbiota Composition.

Zhao, Zhicheng / Li, Chuang / Huang, Jiang / Yuan, Xueying / Cui, Yueqi / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo / Zhang, Zecai

Journal of agricultural and food chemistry

2024 Volume 72, Issue 17, Page(s) 9906–9914

Abstract: Phlorizin (PHZ) is one of the main pharmacologically active ingredients ... ...

Abstract	Phlorizin (PHZ) is one of the main pharmacologically active ingredients in
MeSH term(s)	Animals ; Gastrointestinal Microbiome/drug effects ; Mice ; Cattle ; Bacteria/classification ; Bacteria/isolation & purification ; Bacteria/genetics ; Bacteria/drug effects ; Bovine Virus Diarrhea-Mucosal Disease ; Diarrhea Viruses, Bovine Viral/drug effects ; Antiviral Agents/pharmacology ; Antiviral Agents/administration & dosage ; Feces/microbiology ; Feces/virology ; Female ; Mice, Inbred BALB C ; Male
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.4c01228
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Article: Short‐term treatment with zingerone ameliorates dextran sulfate sodium‐induced mouse experimental colitis

Zhang, Zecai / Cui, Yueqi / Liu, Siyu / Huang, Jiang / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo

Journal of the science of food and agriculture. 2022 Aug. 30, v. 102, no. 11

2022

Abstract: BACKGROUND: Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to ... ...

Abstract	BACKGROUND: Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to investigate the protective effects and potential mechanisms of ZO extracted from ginger on dextran sulfate sodium (DSS)‐induced mouse ulcerative colitis (UC). RESULTS: The results showed that ZO alleviated the weight loss of UC model mice, reduced the disease activity index scores, and inhibited the shortening of colon length. ZO also improved DSS‐induced pathological changes in colon tissue and inhibited the secretion of pro‐inflammatory cytokines in colon and mesenteric lymph nodes. Further mechanism analysis found that ZO inhibited DSS‐induced nuclear factor‐κB pathway activation, and regulated peroxisome proliferator‐activated receptor γ (PPARγ) expression. To further explore whether PPARγ was involved in the anti‐UC effect of ZO, PPARγ inhibitor GW9662 was used. Although ZO also showed a protective effect on GW9662‐treated colitis mice, the protective role was significantly weakened. Importantly, the administration of GW9662 significantly aggravated UC compared with the ZO + DSS group. In addition, we preliminarily found that ZO had the effects of inhibiting DSS‐induced oxidative stress, maintaining intestinal barrier, and inhibiting the content of LPS and the population of Escherichia coli. CONCLUSIONS: These results indicated that supplementation with ZO might be a new dietary strategy for the treatment of UC. © 2022 Society of Chemical Industry.
Keywords	Escherichia coli ; agriculture ; colon ; cytokines ; dextran sulfate ; digestive tract ; ginger ; human health ; lymph ; mice ; oxidative stress ; protective effect ; secretion ; ulcerative colitis ; weight loss
Language	English
Dates of publication	2022-0830
Size	p. 4873-4882.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	184116-6
ISSN	1097-0010 ; 0022-5142
ISSN (online)	1097-0010
ISSN	0022-5142
DOI	10.1002/jsfa.11850
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Short-term treatment with zingerone ameliorates dextran sulfate sodium-induced mouse experimental colitis.

Zhang, Zecai / Cui, Yueqi / Liu, Siyu / Huang, Jiang / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo

Journal of the science of food and agriculture

2022 Volume 102, Issue 11, Page(s) 4873–4882

Abstract: Background: Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to ... ...

Abstract	Background: Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to investigate the protective effects and potential mechanisms of ZO extracted from ginger on dextran sulfate sodium (DSS)-induced mouse ulcerative colitis (UC). Results: The results showed that ZO alleviated the weight loss of UC model mice, reduced the disease activity index scores, and inhibited the shortening of colon length. ZO also improved DSS-induced pathological changes in colon tissue and inhibited the secretion of pro-inflammatory cytokines in colon and mesenteric lymph nodes. Further mechanism analysis found that ZO inhibited DSS-induced nuclear factor-κB pathway activation, and regulated peroxisome proliferator-activated receptor γ (PPARγ) expression. To further explore whether PPARγ was involved in the anti-UC effect of ZO, PPARγ inhibitor GW9662 was used. Although ZO also showed a protective effect on GW9662-treated colitis mice, the protective role was significantly weakened. Importantly, the administration of GW9662 significantly aggravated UC compared with the ZO + DSS group. In addition, we preliminarily found that ZO had the effects of inhibiting DSS-induced oxidative stress, maintaining intestinal barrier, and inhibiting the content of LPS and the population of Escherichia coli. Conclusions: These results indicated that supplementation with ZO might be a new dietary strategy for the treatment of UC. © 2022 Society of Chemical Industry.
MeSH term(s)	Animals ; Colitis/chemically induced ; Colitis/drug therapy ; Colon/metabolism ; Cytokines/metabolism ; Dextran Sulfate ; Disease Models, Animal ; Guaiacol/analogs & derivatives ; Guaiacol/therapeutic use ; Mice ; Mice, Inbred C57BL ; PPAR gamma/genetics ; PPAR gamma/metabolism
Chemical Substances	Cytokines ; PPAR gamma ; zingerone (4MMW850892) ; Guaiacol (6JKA7MAH9C) ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2022-03-23
Publishing country	England
Document type	Journal Article
ZDB-ID	184116-6
ISSN	1097-0010 ; 0022-5142
ISSN (online)	1097-0010
ISSN	0022-5142
DOI	10.1002/jsfa.11850
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Article ; Online: The activation of liver X receptors in Madin-Darby bovine kidney cells and mice restricts infection by bovine viral diarrhea virus.

Cui, Yueqi / Yuan, Xueying / Zhao, Zhicheng / Li, Chuang / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo / Zhang, Zecai

Veterinary microbiology

2023 Volume 288, Page(s) 109948

Abstract: Bovine viral diarrhea virus (BVDV) is prevalent worldwide and is an important pathogen that represents a serious threat to the development of the cattle industry by causing significant economic losses. Liver X receptors (LXRs) are members of the nuclear ... ...

Abstract	Bovine viral diarrhea virus (BVDV) is prevalent worldwide and is an important pathogen that represents a serious threat to the development of the cattle industry by causing significant economic losses. Liver X receptors (LXRs) are members of the nuclear receptor superfamily and have become attractive therapeutic targets for cardiovascular disease. In the present study, we found that LXRs in both Madin-Darby bovine kidney (MDBK) cells and mice were associated with BVDV infection. GW3965, an agonist for LXRs, significantly inhibited BVDV RNA and protein levels in MDBK cells. In vivo studies in a mouse model also confirmed the inhibitory role of GW3965 in BVDV replication and the ameliorating effect of GW3965 on pathological injury to the duodenum. In vitro investigations of the potential mechanisms involved showed that GW3965 significantly inhibited BVDV-induced increases in cholesterol levels and viral internalization. Furthermore, the antiviral activity of GW3965 was significantly reduced following cholesterol replenishment, thus demonstrating that cholesterol was involved in the resistance of GW3965 to BVDV replication. Further studies indicated the role of ATP-binding cassette transporter A1 (ABCA1) and cholesterol-25-hydroxylase (CH25H) in the antiviral activity of GW3965. We also demonstrated the significant antiviral effect of 25hydroxycholesterol (25HC), a product of the catalysis of cholesterol by CH25H. In addition, the anti-BVDV effects of demethoxycurcumin (DMC), cyanidin-3-O-glucoside (C3G), and saikosaponin-A (SSA), three natural agonizts of LXRs, were also confirmed in both MDBK cells and mice. However, the antiviral activities of these agents were weakened by SR9243, a synthetic inhibitor of LXRs. For the first time, our research demonstrated that the activation of LXRs can exert significant anti-BVDV effects in MDBK cells and mice.
MeSH term(s)	Cattle ; Animals ; Mice ; Cell Line ; Liver X Receptors ; Virus Replication/genetics ; Diarrhea Viruses, Bovine Viral/genetics ; Diarrhea Virus 1, Bovine Viral ; Kidney ; Antiviral Agents/pharmacology ; Cholesterol ; Diarrhea/veterinary
Chemical Substances	GW 3965 ; Liver X Receptors ; Antiviral Agents ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-12-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
DOI	10.1016/j.vetmic.2023.109948
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Article ; Online: Phloretin is protective in a murine salmonella enterica serovar typhimurium infection model

Zhang, Zecai / Liu, Siyu / Huang, Jiang / Cui, Yueqi / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo

Microbial Pathogenesis. 2021 Dec., v. 161 p.105298-

2021

Abstract: Salmonella, an important zoonotic pathogen, causes significant morbidity and mortality in both humans and animals. Phloretin mainly isolated from strawberries and apples has the effects of treating inflammation and pathogenic bacteria, but its protective ...

Abstract	Salmonella, an important zoonotic pathogen, causes significant morbidity and mortality in both humans and animals. Phloretin mainly isolated from strawberries and apples has the effects of treating inflammation and pathogenic bacteria, but its protective efficacy and mechanism of action against Salmonella spp. are less clear. In this study, we found that phloretin alleviated body weight loss, colon length shortening, and colonic pathological damage caused by S. Typhimurium. Phloretin also decreased S. Typhimurium translocation to the mesenteric lymph nodes (MLN) and spleen. Further mechanism studies showed that phloretin significantly inhibited inflammation and oxidative stress levels in the colonic tissue. Phloretin also prevented S. Typhimurium-mediated impairment in the colon epithelium barrier by the regulation ZO-1 and occludin levels. Interestingly, phloretin did not inhibit S. typhimurium growth in vitro, but reduced the internalization of S. Typhimurium into Caco-2 cells. Taken together, these findings indicated that phloretin may be a new dietary strategy to combat the disease.
Keywords	Salmonella Typhimurium ; body weight changes ; colon ; epithelium ; inflammation ; lymph ; mechanism of action ; mice ; models ; morbidity ; mortality ; occludins ; oxidative stress ; pathogenesis ; pathogens ; spleen ; Salmonella enterica serover typhimurium ; Phloretin ; Intestinal barrier
Language	English
Dates of publication	2021-12
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2021.105298
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Article ; Online: Phloretin is protective in a murine salmonella enterica serovar typhimurium infection model.

Zhang, Zecai / Liu, Siyu / Huang, Jiang / Cui, Yueqi / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo

Microbial pathogenesis

2021 Volume 161, Issue Pt B, Page(s) 105298

Abstract	Salmonella, an important zoonotic pathogen, causes significant morbidity and mortality in both humans and animals. Phloretin mainly isolated from strawberries and apples has the effects of treating inflammation and pathogenic bacteria, but its protective efficacy and mechanism of action against Salmonella spp. are less clear. In this study, we found that phloretin alleviated body weight loss, colon length shortening, and colonic pathological damage caused by S. Typhimurium. Phloretin also decreased S. Typhimurium translocation to the mesenteric lymph nodes (MLN) and spleen. Further mechanism studies showed that phloretin significantly inhibited inflammation and oxidative stress levels in the colonic tissue. Phloretin also prevented S. Typhimurium-mediated impairment in the colon epithelium barrier by the regulation ZO-1 and occludin levels. Interestingly, phloretin did not inhibit S. typhimurium growth in vitro, but reduced the internalization of S. Typhimurium into Caco-2 cells. Taken together, these findings indicated that phloretin may be a new dietary strategy to combat the disease.
MeSH term(s)	Animals ; Caco-2 Cells ; Humans ; Mice ; Phloretin/pharmacology ; Salmonella Infections, Animal/drug therapy ; Salmonella Infections, Animal/prevention & control ; Salmonella enterica ; Salmonella typhimurium ; Serogroup
Chemical Substances	Phloretin (S5J5OE47MK)
Language	English
Publishing date	2021-11-18
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2021.105298
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Article ; Online: In Vivo and In Vitro Antiviral Activity of Phlorizin Against Bovine Viral Diarrhea Virus.

Zhang, Zecai / Huang, Jiang / Zhao, Zhicheng / Yuan, Xueying / Li, Chuang / Liu, Siyu / Cui, Yueqi / Liu, Yu / Zhou, Yulong / Zhu, Zhanbo

Journal of agricultural and food chemistry

2022 Volume 70, Issue 47, Page(s) 14841–14850

Abstract: Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens affecting the cattle industry worldwide. Phlorizin, a kind of flavonoids extracted from apple tree roots, leaves, and fruits, has a variety of biological functions and has been ... ...

Abstract	Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens affecting the cattle industry worldwide. Phlorizin, a kind of flavonoids extracted from apple tree roots, leaves, and fruits, has a variety of biological functions and has been widely used as a herbal supplement and food additive. Here, BALB/c mouse and Madin-Darby bovine kidney (MDBK) cells were used to explore the effect and mechanism of phlorizin against BVDV infection. The results showed that phlorizin significantly inhibited CP BVDV replication and improved the histopathological changes of duodenum and spleen in mice. In vitro studies also confirmed the activity of phlorizin against CP BVDV. Exploration on its potential mechanism suggested that phlorizin inhibited CP BVDV-induced beclin-1 level and the conversion rate of LC3B-I to LC3B-II. Interestingly, although phlorizin also showed a protective effect on MDBK cells, which were treated with 3-methyladenine A (3-MA), the effect was significantly weakened. Furthermore, phlorizin suppressed the stage of BVDV replication but showed no effect on stages of attachment and internalization. Our data further indicated that phlorizin promoted IFN-α and IFN-β levels, decreased IL-1β and IL-6 expression, and regulated RIG-I, MDA5, TLR3, and NLRP3 levels. Similar to CP BVDV results, in vivo and in vitro, phlorizin inhibited NCP BVDV (NY-1 and YNJG2020 strains) infection. These results were the first to be discovered that phlorizin might be used as a new dietary strategy for controlling BVDV infection.
MeSH term(s)	Animals ; Cattle ; Mice ; Antiviral Agents/pharmacology ; Diarrhea ; Interferon-alpha ; Interferon-beta ; Phlorhizin/pharmacology ; Mice, Inbred BALB C
Chemical Substances	Antiviral Agents ; Interferon-alpha ; Interferon-beta (77238-31-4) ; Phlorhizin (CU9S17279X)
Language	English
Publishing date	2022-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.2c05934
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