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Galacto-oligosaccharides improve barrier function and relieve colonic inflammation via modulating mucosa-associated microbiota composition in lipopolysaccharides-challenged piglets

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Journal of animal Science and Biotechnology 2022年第1期13卷 240-255页

作者： Ren Gao Shiyi Tian Jing Wang Weiyun Zhu National center for International research on animal Gut Nutrition Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal HealthNational Experimental Teaching Demonstration Center of Animal ScienceLaboratory of Gastrointestinal MicrobiologyCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing 210095China

Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported.In this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling piglets.Methods:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS group.Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day.On the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution.All piglets were slaughtered 2 h after intraperitoneal injection and sampled.Results:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its structure.Moreover,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets.In addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling piglets.GOS significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)in the LPS-challenge

关键词： Barrier function Galacto-oligosaccharides Intestinal microbiota Lipopolysaccharides Suckling piglets

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Early-life galacto-oligosaccharides supplementation alleviates the small intestinal oxidative stress and dysfunction of lipopolysaccharide-challenged suckling piglets

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Journal of animal Science and Biotechnology 2022年第5期13卷 1543-1556页

作者： Shiyi Tian Jue Wang Ren Gao Jing Wang Weiyun Zhu Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal HealthNational Center for International Research on Animal Gut NutritionNational Experimental Teaching Demonstration Center of Animal ScienceCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing 210095China

Background:Galacto-oligosaccharides(GOS)are non-digestible food ingredients that promote the growth of beneficial bacteria in the gut.This study investigated the protective effect of the early-life GOS supplement on the piglets’gut function against the oxidative stress induced by lipopolysaccharide(LPS)-challenge.Methods:Eighteen neonatal piglets were assigned to three groups including CON,LPS and LPS+GOS groups.The piglets in CON group and LPS group received physiological saline,while those in LPS+GOS group received GOS solution for 13 d after birth.On d 14,the piglets in LPS group and LPS+GOS group were injected with LPS solutions,while the piglets in CON group were injected with the same volume of physiological saline.Results:The results showed that the early-life GOS supplement blocked the LPS-induced reactive oxygen species(ROS)secretion,malondialdehyde(MDA)production and the increase of pro-apoptotic factor expression.Meanwhile,the early-life GOS supplement improved the activities of antioxidant enzymes,disaccharidase enzymes activities,and digestive enzymes activities,and increased the mRNA abundance of the gene related to nutrient digestion and absorption and the relative protein expression of tight junction.The study also showed that the early-life GOS supplement improved the expression of Hemeoxygenase-1(HO-1)and NAD(P)H/quinone acceptor oxidoreductase-1(NQO-1),and activated the AMP-activated protein kinase(AMPK).Conclusions:These results suggested that GOS enhanced the gut function,reduced the ROS production and proapoptotic factors gene expression,and activated the AMPK signaling pathway in LPS-challenged piglets.

关键词： Early-life Galacto-oligosaccharides Lipopolysaccharide Oxidative stress Suckling piglets

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Responsive changes of rumen microbiome and metabolome in dairy cows with different susceptibility to subacute ruminal acidosis

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animal Nutrition 2022年第1期8卷 331-340页

作者： Tao Zhang Yingyu Mu Ruiyang Zhang Yanfeng Xue Changzheng Guo Wangpan Qi Jiyou Zhang Shengyong Mao National center for International research on animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal ScienceCentre for Ruminant Nutrition and Feed Technology ResearchCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing210095China College of animal Science and Veterinary Medicine Shenyang Agricultural UniversityShenyang110866China College of animal Science and Technology Shihezi UniversityShihezi832000China

Subacute ruminal acidosis(SARA)represents one of the most important digestive disorders in intensive dairy farms,and dairy cows are individually different in the severity of SARA risk.The objectives of the current study were to investigate differences in the ruminal bacterial community and metabolome in dairy cattle with different susceptibility to SARA.In the present study,12 cows were initially enrolled in the experiment.Based on average ruminal pH,4 cows with the lowest ruminal pH were assigned to the susceptible group(SUS,pH=5.76,n=4)and 4 cows with the highest ruminal pH assigned to the tolerant group(TOL,pH=6.10,n=4).Rumen contents from susceptible(SUS,n=4)and tolerant(TOL,n=4)dairy cows were collected through rumen fistula to systematically reveal the rumen microbial and metabolic alterations of dairy cows with different susceptibility to SARA using multi-omics approaches(16S and 18S rRNA gene sequencing and metabolome).The results showed that despite being fed the same diet,SUS cows had lower ruminal pH and higher concentrations of total volatile fatty acids(VFA)and propionate than TOL cows(P0.05).The principal coordinates analysis based on the analysis of molecular variance indicated a significant difference in bacterial composition between the two groups(P=0.01).More specifically,the relative abundance of starch-degrading bacteria(Prevotella spp.)was greater(P0.05).Metabolomics analysis revealed that the concentrations of organic acids(such as lactic acid),biogenic amines(such as histamine),and bacterial degradation prod

关键词： Subacute ruminal acidosis Microbiome Metabolome Dairy cows

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Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

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animal Models and experimental Medicine 2023年第2期6卷 146-154页

作者： Yuhang Sun Bowen Guan Xing Liu Lingyan Zhang Xinpei Wang Aimin Meng Ran Gao National Human Diseases animal Model Resource center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)National Center of Technology Innovation for Animal ModelBeijingChina

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

关键词： angiotensin I converting enzyme busulfan hematopoietic stem cell injury inbred genetic diversity mice urinary marker

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Cellular and molecular characteristics of the premetastatic niches

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animal Models and experimental Medicine 2023年第5期6卷 399-408页

作者： Hongfei Liu Guoxin Zhang Ran Gao Department of Otolaryngology Head and Neck SurgeryBeijing Tongren HospitalCapital Medical UniversityBeijingChina National Human Diseases animal Model Resource center The Institute of Laboratory Animal ScienceChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesBeijingChina Beijing Engineering research center for experimental animal Models of Human Critical Diseases BeijingChina

The premetastatic niches(PMN)formed by primary tumor-derived molecules regulate distant organs and tissues to further favor tumor colonization.Targeted PMN therapy may prevent tumor metastasis in the early stages,which is becoming increasingly important.At present,there is a lack of in-depth understanding of the cellular and molecular characteristics of the PMN.Here,we summarize current research advances on the cellular and molecular characteristics of the PMN.We emphasize that PMN intervention is a potential therapeutic strategy for early prevention of tumor metastasis,which provides a promising basis for future research and clinical application.

关键词： extracellular vesicles immunosuppression premetastatic niches tumor metastasis

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Heterozygous lipoprotein lipase knockout mice exhibit impaired hematopoietic stem/progenitor cell compartment

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animal Models and experimental Medicine 2021年第4期4卷 418-425页

作者： Guiying Shi Xinyue Li Keya Li Yiying Huang Xuepei Lei Lin Bai Chuan Qin The Institute of Laboratory animal Sciences CAMS&PUMCBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesBeijingP.R.China

Background : Hematopoietic stem cells (HSC) maintain the hematopoietic system homeostasis through self- renewal and multilineage differentiation potential. HSC are regulated by the microenvironment, cytokine signaling, and transcription factors. Recent results have shown that lipid pathways play a key role in the regulation of HSC quiescence, proliferation, and division. However, the mechanism by which lipid metabolism regulates HSC proliferation and differentiation remains to be clarified. Lipoprotein lipase (LPL) is an essential enzyme in the anabolism and catabolism of very low- density lipoprotein, chylomicrons, and triglyceride- rich lipoproteins. Methods : The percentage of hematopoietic stem/progenitor cells and immune cells were determined by fluorescence- activated cell sorting (FACS). The function and the mechanism of HSCs were analyzed by cell colony forming assay and qPCR analysis. The changes in LPL^(+/−) HSC microenvironment were detected by transplantation as- says using red fluorescent protein (RFP) transgenic mice. Results : To explore the function of LPL in HSC regulation, heterozygous LPL- knockout mice (LPL^(+/−)) were established and analyzed by FACS. LPL^(+/−) mice displayed decreased hematopoietic stem/progenitor cell compartments. In vitro single- cell clono- genic assays and cell-cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57^(KIP2) and p21^(WAF1)/ ^(CIP1) in LPL^(+/−) mice was upregulated. Conclusions : LPL^(+/−) mice exhibited HSC compartment impairment due to promotion of HSC proliferation, without any effects on the bone marrow (BM) microenvironment.

关键词： cell cycle HSCs LPL

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Effects of high‑grain diet feeding on fatty acid profiles in milk,blood,muscle,and adipose tissue,and transcriptional expression of lipid‑related genes in muscle and adipose tissue of dairy cows

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畜牧与生物技术杂志:英文版 2023年第5期14卷 2063-2078页

作者： Qiaorong Cui Limei Lin Zheng Lai Shengyong Mao Jiangsu Key Laboratory of Gastrointestinal Nutrition and animal Health Laboratory of Gastrointestinal MicrobiologyCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjingJiangsu Province 210095China National center for International research on animal Gut Nutrition Nanjing Agricultural UniversityNanjing 210095China National experimental Teaching Demonstration center of animal Science Nanjing Agricultural UniversityNanjing 210095China

Background High-grain(HG)diets affect lipid metabolism in the liver and mammary tissue of dairy cows,but its effects on muscle and adipose tissue have not been wide evaluated.Thus,the aim of this study is to clarify this issue.Methods Twelve Holstein cows were randomly divided into two groups:conventional diet group(CON,n=6)and the HG diet group(n=6).On day 7 of week 4,rumen fluid was sampled to measure pH,milk was sampled to meas-ure components,and blood was sampled to measure biochemical parameters and fatty acid composition.After the experiment,cows were slaughtered to collect muscle and adipose tissue for fatty acid composition and transcriptome analysis.Results HG feeding decreased the ruminal pH,milk’s fat content and long-chain fatty acid proportion(P<0.05)and increased the proportion of short-and medium-chain fatty acids in the milk(P<0.05)as compared with CON diets.The concentrations of blood cholesterol,low-density lipoprotein,and polyunsaturated fatty acids in the HG cows were lower than those in CON cows(P<0.05).In muscle tissue,HG feeding tended to increase the triacylglycerol(TG)concentration(P<0.10).Transcriptome analysis revealed changes in the biosynthesis of the unsaturated fatty acids pathway,the regulation of lipolysis in the adipocytes pathway,and the PPAR signalling pathway.In adipose tissue,HG feeding increased the concentration of TG and decreased the concentration of C18:1 cis9(P<0.05).At the transcrip-tome level,the fatty acid biosynthesis pathway,linoleic acid metabolism pathway,and PPAR signalling pathway were activated.Conclusion HG feeding leads to subacute rumen acidosis and a decreased milk fat content.The fatty acid profiles in the milk and plasma of dairy cows were changed by HG feeding.In muscle and adipose tissue,HG feeding increased TG concentration and up-regulated the expression of genes related to adipogenesis,while down-regulated the expression of genes related to lipid transport.These results complement our knowledge of the fatty acid composi-tion of muscle and adipose ti

关键词： Adipose tissue Fatty acid composition High-grain diets Lipid transcriptional profiles Muscle tissue

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Anti-apoptotic protein BCL-XL as a therapeutic vulnerability in gastric cancer

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animal Models and experimental Medicine 2023年第3期6卷 245-254页

作者： Yumin Wei Liping Zhang Chao Wang Zefeng Li Mingjie Luo Guomin Xie Xingjiu Yang Mengyuan Li Shuyue Ren Dongbing Zhao Ran Gao Jia-Nan Gong National Human Diseases animal Model Resource center The Institute of Laboratory Animal ScienceChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesBeijingChina Beijing Engineering research center for experimental animal Models of Human Critical Diseases BeijingChina Department of Pancreatic and Gastric Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-Sen UniversityGuangzhouChina

Background: New therapeutic targets are needed to improve the outcomes for gastric cancer(GC) patients with advanced disease. Evasion of programmed cell death(apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the pro-survival BCL2 family proteins represents a promising therapeutic strategy for cancer treatment. Therefore, understanding the molecular mechanisms underpinning cancer cell survival could provide a molecular basis for potential therapeutic interventions. Method: Here we explored the role of BCL2L1 and the encoded anti-apoptotic BCL-XL in GC. Using Droplet Digital PCR(ddPCR) technology to investigate the DNA amplification of BCL2L1 in GC samples and GC cell lines, the sensitivity of GC cell lines to selective BCL-XL inhibitors A1155463 and A1331852, pan-inhibitor ABT-263, and VHL-based PROTAC-BCL-XL was analyzed using(CellTiter-Glo) CTG assay in vitro. Western Blot(WB) was used to detect the protein expression of BCL2 family members in GC cell lines and the manner in which PROTAC-BCL-XL kills GC cells. Coimmunoprecipitation(Co-IP) was used to investigate the mechanism of A1331852 and ABT-263 kills GC cell lines. DDPCR, WB, and real-time PCR(RTPCR) were used to investigate the correlation between DNA, RNA, protein levels, and drug activity. Results: The functional assay showed that a subset of GC cell lines relies on BCL-XL for survival. In gastric cancer cell lines, BCL-XL inhibitors A1155463 and A1331852 are more sensitive than the pan BCL2 family inhibitor ABT-263, indicating that ABT-263 is not an optimal inhibitor of BCL-XL. VHL-based PROTAC-BCL-XL DT2216 appears to be active in GC cells. DT2216 induces apoptosis of gastric cancer cells in a time-and dose-dependent manner through the proteasome pathway. Statistical analysis showed that the BCL-XL protein level predicts the response of GC cells to BCL-XL targeting therapy and BCL2L1 gene CNVs do not reliably predict BCL-XL expression.Conclusion: We identified BCL-XL as a promising therapeutic target in a subset o

关键词： apoptosis BCL2L1(BCL-XL) gastric cancer(GC) PROTAC-BCL-XL selective BCL-XL inhibitors

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Stem cell therapy for Alzheimer’s disease:An overview of experimental models and reality

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animal Models and experimental Medicine 2022年第1期5卷 15-26页

作者： Chuan Qin Kewei Wang Ling Zhang Lin Bai Institute of Laboratory animal Sciences Chinese Academy of Medical Sciences(CAMS)Comparative Medicine CenterPeking Union Medical College(PUMC)NHC Key Laboratory of Human Disease Comparative MedicineKey Laboratory of Human Diseases Animal ModelBeijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases BeijingBeijingChina

Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.

关键词： Alzheimer's disease animal model cognitive deficits memory loss stem cell therapy

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Transcription profiles of skin and head kidney from goldfish suffering hemorrhagic septicemia with an emphasis on the TLR signaling pathway

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Zoological research 2019年第4期40卷 337-342页

作者： Jian-Peng Chen Wei Pang Zi-Wei Zhao Yan-Hui Bi Xiao-Wu Chen National Demonstration center for experimental Fisheries Science Education Shanghai Ocean University Shanghai Engineering research center of Aquaculture Shanghai Collaborative Innovation for Aquatic animal Genetics and Breeding

DEAR EDITOR, Hemorrhagic septicemia is an acute, highly fatal disease that affects goldfish (Carassius auratus). To gain a better understanding of related immune genes, the transcriptomes of the skin and head kidney o... 详细信息

关键词： goldfish suffering hemorrhagic septicemia TLR

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