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Yang T, Lu Z, Song H, Chen Y, Jiang M, Zhan K, Zhao G. Knockout of hexokinase 2 regulates mitochondrial dysfunction and activates the NLRP3 signal pathway in the rumen epithelial cells of dairy cows. Int J Biol Macromol 2025; 289:138831. [PMID: 39701238 DOI: 10.1016/j.ijbiomac.2024.138831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 12/10/2024] [Accepted: 12/14/2024] [Indexed: 12/21/2024]
Abstract
Hexokinase 2 (HK2) plays a vital role in mitochondrial homeostasis; however, the molecular mechanisms underlying its involvement in high-concentrate diet-induced damage in the ruminal epithelium of dairy cows are poorly understood. This study aimed to explore the regulatory role of HK2 in mitochondrial function and responses to inflammation in the rumen of dairy cows fed a high-concentrate diet. Our results showed that, compared with a low-concentrate (LC) diet, feeding a high-concentrate (HC) diet increased oxidative stress and reduced relative antioxidant gene expression levels and enzyme activities in the ruminal epithelium. Furthermore, the expression of genes related to mitochondrial biosynthesis and structure decreased in the HC group, concomitant with nuclear oligomerization domain (NOD)-like receptor 3 (NLRP3) signaling pathway activation, which compromised normal rumen epithelium function. Meanwhile, transcription results showed the same trend in HK2-knockout bovine rumen epithelial cells (HK2KO BRECs) related to wild-type (WT) BRECs. Notably, the knockout of HK2 aggravated mitochondrial dysfunction, resulting in the impairment of mitochondrial morphology and quality, a reduction in mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, increased reactive oxygen species (ROS) generation, and decreased expression of antioxidant genes. These changes led to upregulating genes and proteins in the NLRP3 pathway and activating proinflammatory response. In addition, metabolomic results showed that knockout HK2 altered the glycerophospholipid metabolic pathway. This study provides new strategies for mitigating high-concentrate diet-induced injury in the ruminal epithelium of dairy cows.
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Affiliation(s)
- Tianyu Yang
- Laboratory Animal Center, Xuzhou Medical University, Xuzhou, China; Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Zhiqi Lu
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China; Ningxia Dairy Science and Innovation Center of Bright Farming Company Limited, Zhongwei, China
| | - Han Song
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Yuhang Chen
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Maocheng Jiang
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Kang Zhan
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Guoqi Zhao
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
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Chen W, Ma Q, Li Y, Wei L, Zhang Z, Khan A, Khan MZ, Wang C. Butyrate Supplementation Improves Intestinal Health and Growth Performance in Livestock: A Review. Biomolecules 2025; 15:85. [PMID: 39858479 PMCID: PMC11763988 DOI: 10.3390/biom15010085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/30/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
Butyrate supplementation has gained considerable attention for its potential benefits in livestock, particularly concerning intestinal health and growth performance. This review synthesizes recent research on the diverse roles of butyrate, across various livestock species. As a short-chain fatty acid, butyrate is known for enhancing intestinal development, improving immune function, and modulating microbial diversity. Studies indicate that butyrate supports gut barrier integrity, reduces inflammation, and optimizes feed efficiency, especially during the critical weaning and post-weaning periods in calves, piglets, and lambs. Supplementation with butyrate in livestock has been shown to increase average daily gain (ADG), improve gut microbiota balance, promote growth, enhance gut health, boost antioxidant capacity, and reduce diarrhea. Additionally, butyrate plays a role in the epigenetic regulation of gene expression through histone acetylation, influencing tissue development and immune modulation. Its anti-inflammatory and antioxidant effects have been demonstrated across various species, positioning butyrate as a potential therapeutic agent in animal nutrition. This review suggests that optimizing butyrate supplementation strategies to meet the specific needs of each species may yield additional benefits, establishing butyrate as an important dietary additive for enhancing growth performance and health in livestock.
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Affiliation(s)
- Wenting Chen
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
| | - Qingshan Ma
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
| | - Yan Li
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
| | - Lin Wei
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
| | - Zhenwei Zhang
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
| | - Adnan Khan
- Animal Genomics Laboratory, School of Agriculture and Food Science, University College Dublin, D04 V1W8 Dublin, Ireland;
| | - Muhammad Zahoor Khan
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
| | - Changfa Wang
- School of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China
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He K, Cheng H, McClements DJ, Xu Z, Meng M, Zou Y, Chen G, Chen L. Utilization of diverse probiotics to create human health promoting fatty acids: A review. Food Chem 2024; 458:140180. [PMID: 38964111 DOI: 10.1016/j.foodchem.2024.140180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/09/2024] [Accepted: 06/19/2024] [Indexed: 07/06/2024]
Abstract
Many probiotics produce functional lipids with health-promoting properties, such as short-chain fatty acids, linoleic acid and omega-3 fatty acids. They have been shown to maintain gut health, strengthen the intestinal barrier, and have anti-inflammatory and antioxidant effects. In this article, we provide an up-to-date review of the various functional lipids produced by probiotics. These probiotics can be incorporated into foods, supplements, or pharmaceuticals to produce these functional lipids in the human colon, or they can be used in industrial biotechnology processes to generate functional lipids, which are then isolated and used as ingredients. We then highlight the different physiological functions for which they may be beneficial to human health, in addition to discussing some of the challenges of incorporating probiotics into commercial products and some potential solutions to address these challenges. Finally, we highlight the importance of testing the efficacy and safety of the new generation of probiotic-enhanced products, as well as the great potential for the marketization of related products.
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Affiliation(s)
- Kuang He
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China
| | - Hao Cheng
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China
| | | | - Zhenlin Xu
- School of Food Science and Technology, South China Agricultural University, Guangzhou 510642, China
| | - Man Meng
- Licheng Detection & Certification Group Co., Ltd., Zhongshan 528400, China
| | - Yidong Zou
- Skystone Feed Co., Ltd., Wuxi 214258, China
| | | | - Long Chen
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; State Key Lab of Food Science and Resources, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China; School of Food Science and Technology, South China Agricultural University, Guangzhou 510642, China.
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Zhao W, Shen T, Zhao B, Li M, Deng Z, Huo Y, Aernouts B, Loor JJ, Psifidi A, Xu C. Epigallocatechin-3-gallate protects bovine ruminal epithelial cells against lipopolysaccharide-induced inflammatory damage by activating autophagy. J Anim Sci Biotechnol 2024; 15:109. [PMID: 39118120 PMCID: PMC11311925 DOI: 10.1186/s40104-024-01066-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 06/19/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown. RESULTS In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS. CONCLUSIONS Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.
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Affiliation(s)
- Wanli Zhao
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China
| | - Taiyu Shen
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China
| | - Bichen Zhao
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China
| | - Moli Li
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China
| | - Zhaoju Deng
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China
| | - Yihui Huo
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China
| | - Ben Aernouts
- Department of Biosystems, Division of Animal and Human Health Engineering, KU Leuven University, Kleinhoefstraat 4, Geel, 2440, Belgium
| | - Juan J Loor
- Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Urbana, IL, 61801, USA
| | - Androniki Psifidi
- Department of Clinical Science and Services, Queen Mother Hospital for Animals, The Royal Veterinary College, North Mymms, Hawkshead Lane, Hatfield, Hertfordshire, AL9 7TA, UK
| | - Chuang Xu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China.
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Wang Z, Li L, Li W, Yan H, Yuan Y. Salidroside Alleviates Furan-Induced Impaired Gut Barrier and Inflammation via Gut Microbiota-SCFA-TLR4 Signaling. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:16484-16495. [PMID: 38990698 DOI: 10.1021/acs.jafc.4c02433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.
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Affiliation(s)
- Ziyue Wang
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Lu Li
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Wenliang Li
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Haiyang Yan
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Yuan Yuan
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
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Wang JL, Jing DD. Gastric microbiome and gastric cancer: Relationship, mechanism, and clinical significance. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:327-332. [DOI: 10.11569/wcjd.v32.i5.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
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Muradás TC, Freitas RDS, Gonçalves JIB, Xavier FAC, Marinowic DR. Potential antitumor effects of short-chain fatty acids in breast cancer models. Am J Cancer Res 2024; 14:1999-2019. [PMID: 38859825 PMCID: PMC11162650 DOI: 10.62347/etuq6763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 03/13/2024] [Indexed: 06/12/2024] Open
Abstract
The effects of short-chain fatty acids (SCFAs) have been explored against cancer due to the crosstalk between gut microbiota alterations and the immune system as a crucial role in cancer development. We evaluated the SCFAs effects in both in vitro and in vivo breast cancer models. In vitro, the SCFAs displayed contrasting effects on viability index, according to the evaluation of breast cancer cells with different phenotypes, human MCF-7, SK-BR-3, MDA-MD-231, or the mouse 4T1 lineage. Acetate displayed minimal effects at concentrations up to 100 mM. Alternatively, propionate increases or reduces cell viability depending on the concentration. Butyrate and valerate showed consistent time- and concentration-dependent effects on the viability of human or mouse breast cancer cells. The selective FFA2 4-CMTB or FFA3 AR420626 receptor agonists failed to overtake the SCFA actions, except by modest inhibitory effects on MDA-MB-231 and 4T1 cell viability. The FFA2 CATPB or FFA3 and β-hydroxybutyrate receptor antagonists lacked significant activity on human cell lines, although CATPB reduced 4T1 cell viability. Butyrate significantly affected cell morphology, clonogenicity, and migration, according to the evaluation of MDA-MB-231 and 4T1 cells. A preliminary examination of in vivo oral effects of butyrate, propionate, or valerate, dosed in prophylactic or therapeutic regimens, on several parameters evaluated in an orthotopic breast cancer model showed a reduction of lung metastasis in post-tumor induction butyrate-treated mice. Overall, the present results indicate that in vitro effects of SCFAs did not rely on FFA2 or FFA3 receptor activation, and they were not mirrored in vivo, at least at the tested conditions. Overall, the present results indicate potential in vitro inhibitory effects of SCFAs in breast cancer, independent of FFA2 or FFA3 receptor activation, and, in the metastatic breast cancer model, the butyrate-dosed therapeutic regimen reduced the number of lung metastases.
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Affiliation(s)
- Thaís C Muradás
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do SulPorto Alegre, RS, Brazil
| | - Raquel DS Freitas
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do SulPorto Alegre, RS, Brazil
| | - João IB Gonçalves
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do SulPorto Alegre, RS, Brazil
- Brain Institute of Rio Grande do SulPorto Alegre, RS, Brazil
| | - Fernando AC Xavier
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do SulPorto Alegre, RS, Brazil
- Brain Institute of Rio Grande do SulPorto Alegre, RS, Brazil
| | - Daniel R Marinowic
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do SulPorto Alegre, RS, Brazil
- Brain Institute of Rio Grande do SulPorto Alegre, RS, Brazil
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Suswał K, Tomaszewski M, Romaniuk A, Świechowska-Starek P, Zygmunt W, Styczeń A, Romaniuk-Suswał M. Gut-Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension. J Pers Med 2023; 14:8. [PMID: 38276223 PMCID: PMC10817474 DOI: 10.3390/jpm14010008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/27/2024] Open
Abstract
Recent advancements in the understanding of pulmonary arterial hypertension (PAH) have highlighted the significant role of the gut microbiota (GM) in its pathogenesis. This comprehensive review delves into the intricate relationship between the GM and PAH, emphasizing the influence of gut microbial composition and the critical metabolites produced. We particularly focus on the dynamic interaction between the gut and lung, examining how microbial dysbiosis contributes to PAH development through inflammation, altered immune responses, and changes in the gut-lung axis. Noteworthy findings include variations in the ratios of key bacterial groups such as Firmicutes and Bacteroidetes in PAH and the pivotal roles of metabolites like trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and serotonin in the disease's progression. Additionally, the review elucidates potential diagnostic biomarkers and novel therapeutic approaches, including the use of probiotics and fecal microbiota transplantation, which leverage the gut microbiota for managing PAH. This review encapsulates the current state of research in this field, offering insights into the potential of gut microbiota modulation as a promising strategy in PAH diagnosing and treatment.
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Affiliation(s)
- Konrad Suswał
- Department of Pulmonology, Alergollogy and Oncology, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Michał Tomaszewski
- Department of Cardiology, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Aleksandra Romaniuk
- Cardiology Student Scientific Circle, Academy of Silesia, 40-555 Katowice, Poland;
| | | | - Wojciech Zygmunt
- Department of Pulmonology, Alergollogy and Oncology, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Agnieszka Styczeń
- Department of Cardiology, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Małgorzata Romaniuk-Suswał
- Department of Psychiatry, Psychotheraphy and Early Intervention, Medical University of Lublin, 20-954 Lublin, Poland
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Huang K, Yang B, Xu Z, Chen H, Wang J. The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum. J Anim Sci Biotechnol 2023; 14:130. [PMID: 37821933 PMCID: PMC10568933 DOI: 10.1186/s40104-023-00933-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 08/23/2023] [Indexed: 10/13/2023] Open
Abstract
BACKGROUND Four-chambered stomach including the forestomachs (rumen, reticulum, and omasum) and abomasum allows ruminants convert plant fiber into high-quality animal products. The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants, especially the immune development. However, the dynamics of immune development are poorly understood. RESULTS We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep, at 5, 10, 15, and 25 days of age. We found that forestomachs share similar gene expression patterns, all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25, whereas the metabolic function were significantly downregulated with age. We constructed a cell landscape of the four-chambered stomach using single-cell sequencing. Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells, monocytes and macrophages, as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues. Moreover, the non-immune cells such as epithelial cells play key roles in immune maturation. Cell communication analysis predicted that in addition to immune cells, non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs. CONCLUSIONS Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life. We also identified the gene expression patterns and functional cells associated with immune development. Additionally, we identified some key receptors and signaling involved in immune regulation. These results help to understand the early life immune development at single-cell resolution, which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.
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Affiliation(s)
- Kailang Huang
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058 China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou, 310058 China
| | - Bin Yang
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058 China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou, 310058 China
| | - Zebang Xu
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058 China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou, 310058 China
| | - Hongwei Chen
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058 China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou, 310058 China
| | - Jiakun Wang
- Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310058 China
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, Hangzhou, 310058 China
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Zhen Y, Xi Z, Nasr SM, He F, Han M, Yin J, Ge L, Chen Y, Wang Y, Wei W, Zhang Y, Wang M. Multi-Omics Reveals the Impact of Exogenous Short-Chain Fatty Acid Infusion on Rumen Homeostasis: Insights into Crosstalk between the Microbiome and the Epithelium in a Goat Model. Microbiol Spectr 2023; 11:e0534322. [PMID: 37439665 PMCID: PMC10433986 DOI: 10.1128/spectrum.05343-22] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 06/23/2023] [Indexed: 07/14/2023] Open
Abstract
Emerging data have underscored the significance of exogenous supplementation of butyrate in the regulation of rumen development and homeostasis. However, the effects of other short-chain fatty acids (SCFAs), such as acetate or propionate, has received comparatively less attention, and the consequences of extensive exogenous SCFA infusion remain largely unknown. In our study, we conducted a comprehensive investigation by infusion of three SCFAs to examine their respective roles in regulating the rumen microbiome, metabolism, and epithelium homeostasis. Data demonstrated that the infusion of sodium acetate (SA) increased rumen index while also promoting SCFA production and absorption through the upregulation of SCFA synthetic enzymes and the mRNA expression of SLC9A1 gene. Moreover, both SA and sodium propionate infusion resulted in an enhanced total antioxidant capacity, an increased concentration of occludin, and higher abundances of specific rumen bacteria, such as "Candidatus Saccharimonas," Christensenellaceae R-7, Butyrivibrio, Rikenellaceae RC9 gut, and Alloprevotella. In addition, sodium butyrate (SB) infusion exhibited positive effects by increasing the width of rumen papilla and the thickness of the stratum basale. SB infusion further enhanced antioxidant capacity and barrier function facilitated by cross talk with Monoglobus and Incertae Sedis. Furthermore, metabolome and transcriptome data revealed distinct metabolic patterns in rumen contents and epithelium, with a particular impact on amino acid and fatty acid metabolism processes. In conclusion, our data provided novel insights into the regulator effects of extensive infusion of the three major SCFAs on rumen fermentation patterns, antioxidant capacity, rumen barrier function, and rumen papilla development, all achieved without inducing rumen epithelial inflammation. IMPORTANCE The consequences of massive exogenous supplementation of SCFAs on rumen microbial fermentation and rumen epithelium health remain an area that requires further exploration. In our study, we sought to investigate the specific impact of administering high doses of exogenous acetate, propionate, and butyrate on rumen homeostasis, with a particular focus on understanding the interaction between the rumen microbiome and epithelium. Importantly, our findings indicated that the massive infusion of these SCFAs did not induce rumen inflammation. Instead, we observed enhancements in antioxidant capacity, strengthening of rumen barrier function, and promotion of rumen papilla development, which were facilitated through interactions with specific rumen bacteria. By addressing existing knowledge gaps and offering critical insights into the regulation of rumen health through SCFA supplementation, our study holds significant implications for enhancing the well-being and productivity of ruminant animals.
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Affiliation(s)
- Yongkang Zhen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Zanna Xi
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Shaima Mohamed Nasr
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Feiyang He
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Mengli Han
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural Reclamation Sciences, Shihezi, Xinjiang, People’s Republic of China
| | - Junliang Yin
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural Reclamation Sciences, Shihezi, Xinjiang, People’s Republic of China
| | - Ling Ge
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Yifei Chen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Yusu Wang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Wenjun Wei
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Yihui Zhang
- Experimental Farm of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
| | - Mengzhi Wang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural Reclamation Sciences, Shihezi, Xinjiang, People’s Republic of China
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Meng Z, Tan D, Cheng Z, Jiang M, Zhan K. GPR41 Regulates the Proliferation of BRECs via the PIK3-AKT-mTOR Pathway. Int J Mol Sci 2023; 24:ijms24044203. [PMID: 36835615 PMCID: PMC9963637 DOI: 10.3390/ijms24044203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 02/06/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Short-chain fatty acids (SCFAs) play a pivotal role in regulating the proliferation and development of bovine rumen epithelial cells (BRECs). G protein-coupled receptor 41 (GPR41) is involved in the signal transduction in BRECs as a receptor for SCFAs. Nevertheless, the impact of GPR41 on the proliferation of BRECs has not been reported. The results of this research showed that the knockdown of GPR41 (GRP41KD) decreased BRECs proliferation compared with the wild-type BRECs (WT) (p < 0.001). The RNA sequencing (RNA-seq) analysis showed that the gene expression profiles differed between WT and GPR41KD BRECs, with the major differential genes enriched in phosphatidylinositol 3-kinase (PIK3) signaling, cell cycle, and amino acid transport pathways (p < 0.05). The transcriptome data were further validated by Western blot and qRT-PCR. It was evident that the GPR41KD BRECs downregulated the level of the PIK3-Protein kinase B (AKT)-mammalian target of the rapamycin (mTOR) signaling pathway core genes, such as PIK3, AKT, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) and mTOR contrasted with the WT cells (p < 0.01). Furthermore, the GPR41KD BRECs downregulated the level of Cyclin D2 p < 0.001) and Cyclin E2 (p < 0.05) compared with the WT cells. Therefore, it was proposed that GPR41 may affect the proliferation of BRECs by mediating the PIK3-AKT-mTOR signaling pathway.
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Affiliation(s)
- Zitong Meng
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Dejin Tan
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Zhiqiang Cheng
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Maocheng Jiang
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
| | - Kang Zhan
- Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
- Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
- Correspondence:
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12
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Fock E, Parnova R. Mechanisms of Blood-Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids. Cells 2023; 12:cells12040657. [PMID: 36831324 PMCID: PMC9954192 DOI: 10.3390/cells12040657] [Citation(s) in RCA: 77] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/13/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Impairment of the blood-brain barrier (BBB) integrity is implicated in the numerous neurological disorders associated with neuroinflammation, neurodegeneration and aging. It is now evident that short-chain fatty acids (SCFAs), mainly acetate, butyrate and propionate, produced by anaerobic bacterial fermentation of the dietary fiber in the intestine, have a key role in the communication between the gastrointestinal tract and nervous system and are critically important for the preservation of the BBB integrity under different pathological conditions. The effect of SCFAs on the improvement of the compromised BBB is mainly based on the decrease in paracellular permeability via restoration of junctional complex proteins affecting their transcription, intercellular localization or proteolytic degradation. This review is focused on the revealed and putative underlying mechanisms of the direct and indirect effects of SCFAs on the improvement of the barrier function of brain endothelial cells. We consider G-protein-coupled receptor-mediated effects of SCFAs, SCFAs-stimulated acetylation of histone and non-histone proteins via inhibition of histone deacetylases, and crosstalk of these signaling pathways with transcriptional factors NF-κB and Nrf2 as mainstream mechanisms of SCFA's effect on the preservation of the BBB integrity.
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Affiliation(s)
| | - Rimma Parnova
- Correspondence: ; Tel.: +7-812-552-79-01; Fax: +7-812-552-30-12
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13
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Sha Y, He Y, Liu X, Zhao S, Hu J, Wang J, Li S, Li W, Shi B, Hao Z. Rumen Epithelial Development- and Metabolism-Related Genes Regulate Their Micromorphology and VFAs Mediating Plateau Adaptability at Different Ages in Tibetan Sheep. Int J Mol Sci 2022; 23:ijms232416078. [PMID: 36555715 PMCID: PMC9786296 DOI: 10.3390/ijms232416078] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/09/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
The rumen is an important hallmark organ of ruminants and plays an important role in the metabolism and immune barrier of Tibetan sheep on the Plateau. However, there are few studies on rumen development and metabolism regulation in Tibetan sheep at different ages. Here, we comprehensively analyzed the immune function, fermentation function, rumen epithelial micromorphology and transcriptome profile of Tibetan sheep at different ages. The results showed that the concentration of IgG decreased and the concentration of IgM increased with age (p < 0.05), and the highest concentration of IgA was observed at 1.5 and 3.5 years of age. In terms of rumen fermentation characteristics, VFAs of 4-month-old lambs were the highest, followed by VFAs and NH3-N of Tibetan sheep at 3.5 years of age. Hematoxylin-eosin staining and transmission electron microscopy section examination of rumen epithelial tissue showed that the rumen papilla width increased with age (p < 0.001), the thickness of the stratum corneum decreased, the cells in the stratum corneum showed accelerated migration and the thickness of the rumen muscle layer increased (p < 0.001). Desmosomal junctions between the layers of rumen epithelium increased at 1.5 and 3.5 years old, forming a compact barrier structure, and the basal layer had more mitochondria involved in the regulation of energy metabolism. RNA-seq analysis revealed that a total of 1006 differentially expressed genes (DEGs) were identified at four ages. The DEGs of Tibetan sheep aged 4 months and 6 years were mainly enriched in the oxidation−reduction process and ISG15-protein conjugation pathway. The 1.5 and 3.5-year-olds were mainly enriched in skeletal muscle thin filament assembly, mesenchyme migration and the tight junction pathway. WGCNA showed that DEGs related to rumen microbiota metabolite VFAs and epithelial morphology were enriched in “Metabolism of xenobiotics by cytochrome P450, PPAR signaling pathway, Butanoate metabolism pathways” and participated in the regulation of rumen epithelial immune and fermentation metabolism functions of Tibetan sheep at different ages. This study systematically revealed the regulatory mechanism of rumen epithelial development and metabolism in the plateau adaptation of Tibetan sheep, providing a new approach for the study of plateau adaptation.
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Affiliation(s)
- Yuzhu Sha
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
| | - Yanyu He
- School of Fundamental Sciences, Massey University, Palmerston North 4410, New Zealand
| | - Xiu Liu
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Correspondence: ; Tel.: +86-931-763-1870
| | - Shengguo Zhao
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
| | - Jiang Hu
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
| | - Jiqing Wang
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
| | - Shaobin Li
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
| | - Wenhao Li
- Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining 810000, China
| | - Bingang Shi
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
| | - Zhiyun Hao
- College of Animal Science and Technology/Gansu Key Laboratory of Herbivorous Animal Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
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14
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Na SW, Guan LL. Understanding the role of rumen epithelial host-microbe interactions in cattle feed efficiency. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2022; 10:41-53. [PMID: 35647325 PMCID: PMC9117530 DOI: 10.1016/j.aninu.2022.04.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 02/23/2022] [Accepted: 04/10/2022] [Indexed: 12/22/2022]
Abstract
Feed efficiency is one of the economically important traits for the cattle industry that affects profit (feed costs) and the environment (production of manure and methane). Due to that feed efficiency is driven by multi-factors, mechanisms contributing to the animal to animal variation in this trait have not been well defined, limiting the development of precision feeding strategies to improve the herd production efficiency. Rumen microbial fermentation and volatile fatty acids (VFA) production have been recently reported to be associated with cattle feed efficiency, however the roles of rumen epithelial function in feed efficiency are less studied although the rumen epithelium has an important function in VFA absorption and metabolism which can affect host feed efficiency. Rumen epithelium is colonized with a diverse microbial population, termed epimural microbiota, which has proposed functions in tissue development, barrier and inflammation, urea transport, and oxygen scavenging, suggesting that they can affect rumen epithelial functions and subsequently cattle feed efficiency. Especially, prospective functions of epimural microbiota, enhanced rumen immunity and increased rumen epithelial thickness, might contribute to less nutritional requirement for tissue recuperation. Thus, the understanding of the functions of rumen epithelium, epimural microbiota, and rumen epithelial host-microbe interactions is essential to identify their roles in contributing to feed efficiency. In this review, we will focus on to date research findings on the structure of rumen epithelium, epimural microbiota, and epithelial host-microbe interactions together with their functions and how these are associated with feed efficiency, aiming to provide insights on future directions to study rumen epithelial host-microbe interactions and improve the rumen functions in cattle.
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Affiliation(s)
- Sang Weon Na
- Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Le Luo Guan
- Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
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Zhang X, Liu W, Zhang S, Wang J, Yang X, Wang R, Yan T, Wu B, Du Y, Jia Y. Wei-Tong-Xin ameliorates functional dyspepsia via inactivating TLR4/MyD88 by regulating gut microbial structure and metabolites. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 102:154180. [PMID: 35613516 DOI: 10.1016/j.phymed.2022.154180] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/23/2022] [Accepted: 05/16/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Wei-Tong-Xin (WTX) is a traditional Chinese medicine (TCM) that has been screened and improved in accordance with the famous ancient Chinese formula "Wan Ying Yuan". It has been shown to be clinically effective in treating gastric dysmotility, but its underlying molecular mechanism remains unclear. PURPOSE This study primarily dealt with the effects and mechanisms of WTX on functional dyspepsia (FD) induced by chemotherapeutic drug cisplatin (CIS). METHODS Firstly, the UPLC fingerprint and multi-component determination of WTX were established. In vivo, gastrointestinal motility of mice was detected by charcoal propulsion test. Besides, H&E, western blot and qRT-PCR were performed to evaluate the occurrence of gastric antral inflammation. ROS-DHE staining was used to detect ROS levels. Further, the gut microbiota were subjected to sequencing by 16S rRNA, and the levels of bacterial metabolites short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) were detected by GC-MS and Limulus kits, respectively. The levels of GLP-1 in gastric antrum were assessed by ELISA kits. Finally, siRNA-FFAR2 experiment was performed in Raw 264.7 cells. RESULTS 23 common peaks were obtained from the UPLC fingerprint, and the content of 10 target components was determined. WTX increased the relative abundance of Firmicutes and decreased the number of Verrucomicrobia, accompanied by changes in the levels of SCFAs and LPS. By mediating the expression changes of free fatty acid receptor 2 (FFAR2) and toll-like receptor 4 (TLR4), WTX inhibited the phosphorylation of nuclear factor-κB (NF-κB), JNK and P38, decreased the levels of IL-1β, inducible nitric oxide synthase (iNOS) and ROS, increased the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), IL-4 and arginase-1 (Arg-1). Decreased expressions of glucagon-like peptide 1 (GLP-1) induced by WTX promoted gastric motility in FD mice. In vitro, siRNA-FFAR2 of Raw 264.7 cells eliminated the effects of WTX on TLR4 signaling pathway. CONCLUSIONS In this study, the chemical profile of WTX was first reported. Based on remodeling the gut microbiota structure and adjusting the levels of metabolites (SCFAs and LPS), WTX inactivated the TLR4/MyD88 signaling pathway to inhibit the occurrence of gastric antral inflammation, which reversed the inhibitory effect of GLP-1 on gastric motility, and improved CIS-induced FD symptoms.
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Affiliation(s)
- Xiaoying Zhang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Wenjuan Liu
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Shuanglin Zhang
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Jinyu Wang
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Xihan Yang
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Ruixuan Wang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Tingxu Yan
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Bo Wu
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China
| | - Yiyang Du
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.
| | - Ying Jia
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.
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16
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Guo L, Wang Z, Li J, Li J, Cui L, Dong J, Meng X, Qian C, Wang H. Immortalization effect of SV40T lentiviral vectors on canine corneal epithelial cells. BMC Vet Res 2022; 18:181. [PMID: 35578336 PMCID: PMC9109393 DOI: 10.1186/s12917-022-03288-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 05/10/2022] [Indexed: 11/10/2022] Open
Abstract
Background Primary canine corneal epithelial cells (CCECs) easily become senescent, and cell proliferation is limited. Therefore, sampling for experimentation requires a large number of animals, which is problematic in terms of animal welfare and fails to maintain the stability of the cells for in vitro analyses. Results In this study, CCECs were separated and purified by trypsin and dispase II enzymatic analysis. Next, the cells were immortalized by transfection with a lentiviral vector expressing Simian vacuolating virus 40 large T (SV40T). The immortalized canine corneal epithelial cell line (CCEC-SV40T) was established by serial passages and monoclonal selection. The biological characteristics of CCEC-SV40T cells were evaluated based on the cell proliferation rate, cell cycle pattern, serum dependence, karyotype, and cytokeratin 12 immunofluorescence detection. In addition, we infected CCEC-SV40T cells with Staphylococcus pseudintermedius (S. pseudintermedius) and detected the inflammatory response of the cells. After the CCEC-SV40T cells were passaged continuously for 40 generations, the cells grew in a cobblestone pattern, which was similar to CCECs. The SV40T gene and cytokeratin 12 can be detected in each generation. CCEC-SV40T cells were observed to have a stronger proliferation capacity than CCECs. CCEC-SV40T cells maintained the same diploid karyotype and serum-dependent ability as CCECs. After CCEC-SV40T cells were infected with S. pseudintermedius, the mRNA expression levels of NLRP3, Caspase-1 and proinflammatory cytokines, including IL-1β, IL-6, IL-8 and TNF-α, were upregulated, and the protein levels of MyD88, NLRP3 and the phosphorylation of Iκbα and p65 were upregulated. Conclusions In conclusion, the CCEC-SV40T line was successfully established and can be used for in vitro studies, such as research on corneal diseases or drug screening. Supplementary Information The online version contains supplementary material available at 10.1186/s12917-022-03288-3.
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Affiliation(s)
- Long Guo
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Zhihao Wang
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Jun Li
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Jianji Li
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Luying Cui
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Junsheng Dong
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Xia Meng
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Chen Qian
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China
| | - Heng Wang
- College of Veterinary Medicine, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, Jiangsu, China. .,Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education, Yangzhou, 225009, Jiangsu, China.
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Wang K, Lei Q, Ma H, Jiang M, Yang T, Ma Q, Datsomor O, Zhan K, Zhao G. Phloretin Protects Bovine Rumen Epithelial Cells from LPS-Induced Injury. Toxins (Basel) 2022; 14:toxins14050337. [PMID: 35622584 PMCID: PMC9147548 DOI: 10.3390/toxins14050337] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/08/2022] [Accepted: 05/09/2022] [Indexed: 12/04/2022] Open
Abstract
Lipopolysaccharide (LPS) is an endotoxin that induces immune and inflammatory responses in the rumen epithelium of dairy cows. It is well-known that flavonoid phloretin (PT) exhibits anti-oxidative, anti-inflammatory and antibacterial activity. The aim of this research was to explore whether PT could decrease LPS-induced damage to bovine rumen epithelial cells (BRECs) and its molecular mechanisms of potential protective efficacy. BRECs were pretreated with PT for 2 h and then stimulated with LPS for the assessment of various response indicators. The results showed that 100 µM PT had no significant effect on the viability of 10 µg/mL LPS-induced BRECs, and this dose was used in follow-up studies. The results showed that PT pre-relieved the decline in LPS-induced antioxidant indicators (T-AOC and GSH-PX). PT pretreatment resulted in decreased interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α) and chemokines (CCL2, CCL5, CCL20) expression. The underlying mechanisms explored reveal that PT may contribute to inflammatory responses by regulating Toll-like receptor 4 (TLR4), nuclear transcription factor-κB p65 (NF-κB p65), and ERK1/2 (p42/44) signaling pathways. Moreover, further studies found that LPS-induced BRECs showed decreased expression of claudin-related genes (ZO-1, Occludin); these were attenuated by pretreatment with PT. These results suggest that PT enhances the antioxidant properties of BRECs during inflammation, reduces gene expression of pro-inflammatory cytokines and chemokines, and enhances barrier function. Overall, the results suggest that PT (at least in vitro) offers some protective effect against LPS-induced ruminal epithelial inflammation. Further in vivo studies should be conducted to identify strategies for the prevention and amelioration of short acute rumen acidosis (SARA) in dairy cows using PT.
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Yang T, Datsomor O, Jiang M, Ma X, Zhao G, Zhan K. Protective Roles of Sodium Butyrate in Lipopolysaccharide-Induced Bovine Ruminal Epithelial Cells by Activating G Protein-Coupled Receptors 41. Front Nutr 2022; 9:842634. [PMID: 35600833 PMCID: PMC9121101 DOI: 10.3389/fnut.2022.842634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 03/10/2022] [Indexed: 11/13/2022] Open
Abstract
This study aimed to evaluate whether sodium butyrate (SB) attenuates the ruminal response to LPS-stimulated inflammation by activating GPR41 in bovine rumen epithelial cells (BRECs). We examined the SB regulation of GPR41 and its impact on LPS-induced inflammation using GPR41 knockdown BRECs. The LPS-induced BRECs showed increases in the expression of genes related to pro-inflammation and decreases in the expression of genes related to tight junction proteins; these were attenuated by pretreatment with SB. Compared with that in LPS-stimulated BRECs, the ratio of phosphorylated NF-κB (p65 subunit) to NF-κB (p65 subunit) and the ratio of phosphorylated IκBα to IκBα were suppressed with SB pretreatment. The LSB group abated LPS-induced apoptosis and decreased the expression of Bax, Caspase 3, and Caspase 9 mRNA relative to the LPS group. In addition, the LSB group had a lower proportion of cells in the G0–G1 phase and a higher proportion of cells in the S phase than the LPS group. The mRNA expression of ACAT1 and BDH1 genes related to volatile fatty acid (VFA) metabolism were upregulated in the LSB group compared to those in LPS-induced BRECs. In addition, pretreatment with SB promoted the gene expression of GPR41 in the LPS-induced BRECs. Interestingly, SB pretreatment protected BRECs but not GPR41KD BRECs. Our results suggest that SB pretreatment protects against the changes in BRECs LPS-induced inflammatory response by activating GPR41.
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19
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Wu P, Zhu T, Tan Z, Chen S, Fang Z. Role of Gut Microbiota in Pulmonary Arterial Hypertension. Front Cell Infect Microbiol 2022; 12:812303. [PMID: 35601107 PMCID: PMC9121061 DOI: 10.3389/fcimb.2022.812303] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 03/30/2022] [Indexed: 11/13/2022] Open
Abstract
Gut microbiota and its metabolites play an important role in maintaining host homeostasis. Pulmonary arterial hypertension (PAH) is a malignant clinical syndrome with a frightening mortality. Pulmonary vascular remodeling is an important feature of PAH, and its pathogenesis is not well established. With the progress of studies on intestinal microbes in different disease, cumulative evidence indicates that gut microbiota plays a major role in PAH pathophysiology. In this review, we will systematically summarize translational and preclinical data on the correlation between gut dysbiosis and PAH and investigate the role of gut dysbiosis in the causation of PAH. Then, we point out the potential significance of gut dysbiosis in the diagnosis and treatment of PAH as well as several problems that remain to be resolved in the field of gut dysbiosis and PAH. All of this knowledge of gut microbiome might pave the way for the extension of novel pathophysiological mechanisms, diagnosis, and targeted therapies for PAH.
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20
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Growth Performance, Rumen Fermentation and Inflammatory Response on Holstein Growing Cattle Treated with Low and High Non-Fibrous Carbohydrate to Neutral Detergent Fiber Ratio Pelleted Total Mixed Ration. Animals (Basel) 2022; 12:ani12081036. [PMID: 35454282 PMCID: PMC9026707 DOI: 10.3390/ani12081036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/12/2022] [Accepted: 04/13/2022] [Indexed: 12/10/2022] Open
Abstract
Twenty-four healthy castrated male Holstein growing cattle, with similar body weight (301 ± 11.5 kg), were enrolled in this study and randomly allocated into two groups (12/pen). Holstein growing cattle in the LPT (low NFC/NDF pelleted TMR) group were fed basal pelleted TMR with a low NFC/NDF ratio (NFC/NDF = 1.07), while the HPT (high NFC/NDF pelleted TMR) group were fed with a high NFC/NDF ratio diet (NFC/NDF = 1.71). The results showed that: (1) Body measurements were found to be increased for the LPT group (p < 0.05); compared with the HPT group, feed intake to gain ratio and feed cost in the LPT group were decreased by 12.24% and 15.35%, respectively (p < 0.01). Compared with the HPT group, the LPT group tended to increase chest girth. (2) Digestibility of DM and NDF in the LPT group was higher (p < 0.05) than in the HPT group, being increased by 3.41% and 4.26%, respectively, and increased digestibility of ADF in the LPT group was significant (p < 0.01). (3) The daily feed consumption of NDF in the LPT group was higher than that in the HPT group and the daily rumination time and chewing time in the LPT group were longer than that in the HPT group (p < 0.05). (4) Compared with the LPT group, the parameter of pH, microbial protein and acetate: propionate (p < 0.05) in the HPT group were decreased by 8.57%, 12.46% and 23.71%, respectively. In contrast, the concentration of total volatile fatty acids, acetate and propionate were higher (p < 0.05) in the HPT group, and increased by 13.49%, 19.59% and 52.70%, respectively. (5) Compared with the LPT group, rumen fluid in the HPT group diet up-regulated the mRNA expression levels of BRECs pro-inflammatory factor IL-1β and TNF-α (p < 0.05), and meanwhile, up-regulated the mRNA expression levels of BRECs pro-inflammatory factor IL-6 (p < 0.01); compared with the LPT group, rumen fluid in the HPT group diet up-regulated the mRNA expression levels of CCL28 and CCL20 (p < 0.05) chemokines in CCL types of BRECs; in addition, compared with the LPT group, rumen fluid in the HPT group up-regulated the mRNA expression levels of CXCL2, CXCL3, CXCL9 and CXCL14 chemokines in CXCL types of BRECs (p < 0.01), and the mRNA expression levels of the CXCL5 chemokine tended to be increased (p = 0.06).
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Establishment of Immortalized Yak Ruminal Epithelial Cell Lines by Lentivirus-Mediated SV40T and hTERT Gene Transduction. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8128028. [PMID: 35368868 PMCID: PMC8975702 DOI: 10.1155/2022/8128028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/27/2022] [Accepted: 03/09/2022] [Indexed: 12/01/2022]
Abstract
Yak is a unique species of cattle that is adapted to the harsh natural environment of the Qinghai-Tibet Plateau. Research on the function of the yak rumen is limited to animal experiments, and the cell molecular mechanism is very limited. The high cost of isolation and culture of adult yak rumen epithelial cells (YRECs), low success rate, and limited cell life limit the scope of long-term physiological functions and nutrient absorption mechanisms of yak rumen epithelium in vitro studies. This study aimed to explore the isolation and immortal culture methods of primary YRECs and establish a new cell line model for studying cell molecular mechanisms. The human telomerase reverse transcriptase gene (hTERT) and simian virus 40 large T antigen (SV40T) were transferred into primary YDECs using mammalian gene expression lentiviral vectors. The immortalized cell line (SV40T-YREC-hTERT) retains the morphological and functional characteristics of primary cells. The epithelial cell marker protein cytokeratin 18 of the immortalized cell lines was positive, and the cell proliferation and karyotype were normal. The SV40T and hTERT genes were successfully transferred into immortalized cell lines and maintained high expression. Simultaneously, the immortalized cell lines had normal function of short-chain fatty acid (SCFA) transport and absorption, and the immortalized yak rumen epithelial cell lines were successfully established. In addition, the transepithelial electrical resistance value gradually increased with culture time, and the permeability of epithelial cells decreased by culturing epithelial cells in Transwell culture chambers. Transmission electron microscopy demonstrated the submicroscopic structure of cells in the integrity barrier model and established the YREC barrier model in vitro.
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22
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Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2022; 8:350-360. [PMID: 35510031 PMCID: PMC9040132 DOI: 10.1016/j.aninu.2021.11.005] [Citation(s) in RCA: 133] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 02/07/2023]
Abstract
Gut inflammation is a challenging concern in humans and animals, which disturbs normal growth and leads to severe bowel diseases. Short chain fatty acids (SCFA) are the gut microbiota metabolites produced from fermentation of non-digestible carbohydrates, and have been reported to modulate gut inflammation. SCFA have been implicated as the potential therapeutic bioactive molecules for gut inflammatory diseases, and could be an alternative to antibiotic growth promoters (AGP). In this review, the existing knowledge about the types of SCFA, the related gut microbes producing SCFA, the roles of SCFA in maintaining gut homeostasis, and how SCFA modulate gut inflammation is summarized. The therapeutic application of SCFA in the treatment of inflammatory bowel disease (IBD) is also highlighted.
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23
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Hua Q, Han Y, Zhao H, Zhang H, Yan B, Pei S, He X, Li Y, Meng X, Chen L, Zhong F, Li D. Punicalagin alleviates renal injury via the gut-kidney axis in high-fat diet-induced diabetic mice. Food Funct 2022; 13:867-879. [PMID: 34989745 DOI: 10.1039/d1fo03343c] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Diabetic renal injury was associated with dysbiosis of the gut microbiota and intestinal barrier. Punicalagin (PU) from pomegranates potentially impacts the microbial ecosystem, intestinal barrier, and renal function. Therefore, we hypothesized that PU may improve diabetic renal injury by modulating the gut-kidney axis. The present study evaluated the effect of PU on the gut-kidney axis and kidney function in a diabetic renal injury mouse model induced by a high-fat diet (HFD). Mice were fed a HFD without PU or with at doses of 50 and 100 mg kg-1 d-1 for 8 weeks. Targeted metabolomics by GC-MS and 16S rRNA sequencing were implemented to determine short-chain fatty acids (SCFAs) and microbes. Further RNA sequencing analyses were performed to determine which differentially expressed genes were changed by PU. Compared with the DM model group, PU supplementation improved diabetic renal injury, ameliorated kidney architecture and function, and reshaped gut microbial ecology. Additionally, PU reversed HFD-induced gut barrier dysfunction, promoted cecal SCFA concentrations and inhibited serum lipopolysaccharide (LPS) and diamine oxidase (DAO) levels. Moreover, correlation analysis found that cecal SCFAs were significantly negatively correlated with inflammation-related genes in the kidney. The present results indicated that PU, a promising bioactive polyphenol, successfully improved diabetic renal injury, most likely through the gut-kidney axis.
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Affiliation(s)
- Qinglian Hua
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Yaling Han
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Haifeng Zhao
- Qingdao Institute for Food and Drug Control, Qingdao, China
| | - Haowen Zhang
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Bei Yan
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Shengjie Pei
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Xin He
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Yue Li
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Xiangyuan Meng
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Lei Chen
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Feng Zhong
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
| | - Duo Li
- School of Public health, Qingdao University, Qingdao, China. .,Institute of Nutrition & Health, Qingdao University, Qingdao, China
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24
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Zhang Z, Han Z, Guo Y, Liu X, Gao Y, Zhang Y. Establishment of an Efficient Immortalization Strategy Using HMEJ-Based b TERT Insertion for Bovine Cells. Int J Mol Sci 2021; 22:ijms222212540. [PMID: 34830422 PMCID: PMC8622252 DOI: 10.3390/ijms222212540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 12/09/2022] Open
Abstract
Immortalized cell lines have been used in a wide range of applications in research on immune disorders and cellular metabolic regulation due to the stability and uniformity of their cellular characteristics. At present, the investigation into molecular functions and signaling pathways within bovine cells remains largely limited by the lack of immortalized model cells. Current methods for immortalizing bovine cells are mainly restricted to the ectopic expression of human telomerase reverse transcriptase (hTERT) through transient transfection or virus-mediated delivery, which have defects in efficiency and reliability. In this study, we identified bovine TERT (bTERT) as a novel potent biofactor for immortalizing bovine cells with great advantages over hTERT, and established an efficient and easily manipulated strategy for the immortalization of bovine primary cells. Through the homology-mediated end-joining-based insertion of bTERT at the ROSA26 locus, we successfully generated immortalized bovine fetal fibroblast cell lines with stable characteristics. The observed limitation of this strategy in immortalizing bovine bone marrow-derived macrophages was attributed to the post-translational modification of bTERT, causing inhibited nuclear localization and depressed activity of bTERT in this terminally differentiated cell. In summary, we constructed an innovative method to achieve the high-quality immortalization of bovine primary cells, thereby expanding the prospects for the future application of immortalized bovine model cell lines.
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Affiliation(s)
- Zihan Zhang
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China; (Z.Z.); (Z.H.); (Y.G.); (X.L.)
- Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Xianyang 712100, China
| | - Zhuo Han
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China; (Z.Z.); (Z.H.); (Y.G.); (X.L.)
- Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Xianyang 712100, China
| | - Ying Guo
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China; (Z.Z.); (Z.H.); (Y.G.); (X.L.)
- Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Xianyang 712100, China
| | - Xin Liu
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China; (Z.Z.); (Z.H.); (Y.G.); (X.L.)
- Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Xianyang 712100, China
| | - Yuanpeng Gao
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China; (Z.Z.); (Z.H.); (Y.G.); (X.L.)
- Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Xianyang 712100, China
- Correspondence: (Y.G.); (Y.Z.)
| | - Yong Zhang
- College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China; (Z.Z.); (Z.H.); (Y.G.); (X.L.)
- Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Xianyang 712100, China
- Correspondence: (Y.G.); (Y.Z.)
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25
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Dang G, Wu W, Zhang H, Everaert N. A new paradigm for a new simple chemical: butyrate & immune regulation. Food Funct 2021; 12:12181-12193. [PMID: 34752597 DOI: 10.1039/d1fo02116h] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Short-chain fatty acids (SCFAs) play an important role in the host system. Among SCFAs, butyrate has received particular attention for its large effect on host immunity, particularly in supplying energy to enterocytes and producing immune cells. Butyrate enters the cells through the Solute Carrier Family 5 Member 8 (SLC5A8) transporters, then works as a histone deacetylase inhibitor (HDAC) that inhibits the activation of Nuclear factor-κB (NF-κB), which down-regulates the expression of IL-1β, IL-6, TNF-α. Meanwhile, butyrate acts as a ligand to activate G protein-coupled receptors GPR41, GPR43, and GPR109, promoting the expression of anti-inflammatory factors. Besides, it inhibits the proinflammatory factors. Further, it can also suppress the expression of chemokines and reduce inflammation to maintain host homeostasis. This paper reviews the research progress highlighting the potential function of butyrate as a factor impacting intestinal health, obesity and brain disorders.
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Affiliation(s)
- Guoqi Dang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. .,Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Liège University, Passage des Déportés 2, Gembloux, Belgium
| | - Weida Wu
- Institute of Quality Standard & Testing Technology for Agro-Products, Key Laboratory of Agro-product Quality and Safety, Chinese Academy of Agricultural Sciences, Beijing 100081, PR China
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
| | - Nadia Everaert
- Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Liège University, Passage des Déportés 2, Gembloux, Belgium
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26
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Ginkgo Biloba L. Residues Partially Replacing Alfalfa Hay Pellet in Pelleted Total Mixed Ration on Growth Performance, Serum Biochemical Parameters, Rumen Fermentation, Immune Function and Meat Quality in Finishing Haimen White Goats. Animals (Basel) 2021; 11:ani11113046. [PMID: 34827778 PMCID: PMC8614405 DOI: 10.3390/ani11113046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/17/2021] [Accepted: 10/21/2021] [Indexed: 11/17/2022] Open
Abstract
Sixty castrated male Haimen white growing goats with an initial age of 100 days old and similar body weight (16 ± 1.5 kg) were selected and randomly allocated into five groups with three replicates in each group with four goats in each pen (5 m × 3.2 m). Goats in the control group (CG) were fed a basal pelleted total mixed ration supplemented with 30% alfalfa hay pellet, while experimental treatments (G6, G12, G18, or G24) were supplemented with four levels (6%, 12%, 18%, or 24%) of GBLR replacing alfalfa hay pellet in the diet, separately. Results showed that (1) the final body weight, average daily gain, and average feed intake of G18 was significantly higher (p < 0.05) than CG; in contrast, the feed conversion ratio of G18 was significantly lower than CG and G12 (p < 0.05); the feed cost per head per day of CG was significantly higher (p < 0.05) than that of G18 and G24, and exhibited obvious linearly decrease (p = 0.04) with increasing GBLR supplementation; and apparent total-tract digestibility of DM and NDF in GBLR treatments were significantly higher (p < 0.05) than CG; (2) alanine transaminase (ALT) concentration in the G18 group was significantly lower (p < 0.05) than those in the control group; aspartate transaminase (AST) concentration in the G24 was significantly lower (p < 0.05) than those in the control group, and an increase in dietary level of GBLR tended to result in a linear decrease (p = 0.09) in the concentration of serum AST; (3) the concentration of malondialdehyde (MDA) demonstrated a tendency to decrease (p = 0.06) linearly with increasing GBLR supplementation; however, glutathione peroxidase (GSH-PX) activity in G12 was significantly higher (p < 0.05) than CG, G6, and G24; in addition, superoxide dismutase (SOD) activity in G18 was significantly higher (p < 0.05) than CG and G6; concentration of immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA) were not affected by GBLR, but increasing dietary GBLR showed a tendency (p = 0.08) to linearly increase the IgG concentration; the content of interleukin 4 (IL4) was significantly higher (p < 0.05) in G12, G18, and G24 than that in CG and G6; (4) There were similar NH3-N, pH, TVFA, and butyrate for goats fed different levels of GBLR supplementation; the C2 (p = 0.07) and acetate: propionate (p = 0.06) demonstrated a tendency to increase linearly with increasing level of GBLR supplementation, separately; however, it was observed that concentration of propionate showed a tendency to decrease (p = 0.08) linearly in response to GBLR supplementation; and (5) Increasing dietary GBLR tended to linearly enhance the lightness (L*) (p = 0.07) and yellowness (b*) (p = 0.09) values of longissimus dorsi muscles; the redness (a*) value in G18 was significantly higher than that in CG (p < 0.05).
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27
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Hu Z, Lin M, Ma X, Zhao G, Zhan K. Effect of Tea Tree Oil on the Expression of Genes Involved in the Innate Immune System in Goat Rumen Epithelial Cells. Animals (Basel) 2021; 11:ani11082460. [PMID: 34438917 PMCID: PMC8388664 DOI: 10.3390/ani11082460] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 08/14/2021] [Accepted: 08/19/2021] [Indexed: 11/26/2022] Open
Abstract
Simple Summary Subacute rumen acidosis (SARA) often causes significant losses on commercial farms. SARA is mainly caused by endotoxin (LPS) produced by the lysis of Gram-negative bacteria, which causes an inflammatory response. To alleviate the inflammatory response mediated by LPS, it is important to improve animal production performance. Tea tree oil (TTO) is a plant extract that possesses good bactericidal and anti-inflammatory effects. According to this study, LPS can significantly induce inflammatory responses in goat rumen epithelial cells (GRECs), while the addition of TTO could markedly mitigate inflammatory responses mediated by LPS in GRECs. Therefore, it may be useful for the treatment of SARA. Abstract In subacute rumen acidosis (SARA), the rumen epithelium is frequently attacked by endotoxin (LPS), which is caused by the lysis of dead Gram-negative bacteria. However, the rumen epithelium innate immune system can actively respond to the infection. Previous studies have demonstrated that tea tree oil (TTO) has good bactericidal and anti-inflammatory effects. Therefore, the aim of this study was to investigate the effect of TTO on the expression of genes involved in the inflammatory cytokines in goat rumen epithelial cells (GRECs) triggered by LPS. Our study shows that rumen epithelial cells isolated from goat rumen tissue can be cultured in vitro in 0.25% trypsin for a long time. These cells were identified as epithelial cells by the expression of cytokeratin 18, monocarboxylate transporter 4 (MCT4), Na[+]/H[+] hydrogen exchanger 1 (NHE1), putative anion transporter 1 (PAT1), vH+ ATPase B subunit (vH+ ATPase), and anion exchanger 2 (AE2). The mRNA expression of IL-1β, IL-6, TNF-α, TLR-2, NF-κB, CXCL6 and CXCL8 genes was significantly increased when LPS was used compared to untreated controls. In addition, mRNA expression of IL-1β, IL-6, TNF-α, TLR-2, NF-κB, CXCL8, CXCL6 and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) genes was also significantly higher in the LPS group compared to the 0.05% TTO group. However, the expression of IL-1β, IL-6, TNF-α, TLR-2, CXCL6 and IFIT3 genes was significantly lower in the LPS and 0.05% TTO group compared to the 1 μg/mL LPS group. These results suggest that TTO can inhibit LPS-induced inflammatory cytokines expression in GRECs.
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Affiliation(s)
| | | | | | | | - Kang Zhan
- Correspondence: ; Tel.: +86-188-5272-0422
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28
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Yang C, Zhu B, Ye S, Fu Z, Li J. Isomer-Specific Effects of cis-9, trans-11- and trans-10, cis-12-CLA on Immune Regulation in Ruminal Epithelial Cells. Animals (Basel) 2021; 11:ani11041169. [PMID: 33921651 PMCID: PMC8072642 DOI: 10.3390/ani11041169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/08/2021] [Accepted: 04/15/2021] [Indexed: 11/23/2022] Open
Abstract
Simple Summary The significant contribution of rumen microbiota to the balance of the innate immunity of rumen epithelium has been extensively verified. As the natural rumen microbial metabolites, information regarding the immunoprotective effects of different conjugated linoleic acid (CLA) isomers on ruminal epithelial cells (RECs) is limited. In this study, the 100 μM trans-10,cis-12-CLA exerted better anti-inflammatory effects than the cis-9,trans-11-CLA by significantly downregulating the expression of genes related to inflammation, cell proliferation and migration in RECs upon lipopolysaccharide (LPS) stimulation. The trans-10,cis-12-CLA, but not cis-9,trans-11-CLA, significantly suppressed the biological signals of gene ontology (GO) terms’ response to lipopolysaccharide, the regulation of signal transduction and cytokine production and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways NF-κB, chemokine, NOD-like receptor, Hippo, PI3K-Akt, TGF-β and Rap1 signaling in RECs upon LPS stimulation. Furthermore, pretreatment with trans-10,cis-12-CLA significantly reduced the expression of lipogenic genes and the biosynthesis of the unsaturated fatty acid pathway in RECs compared with the LPS group, however, cis-9,trans-11-CLA exhibited the opposite results. These results suggest the distinct isomer differences of CLA in the regulation of inflammatory responses and adipocytokine signaling in RECs and will provide important references for determining their target use in the future. Abstract In this study, we used transcriptomics and qPCR to investigate the potential immunoprotective effects of different conjugated linoleic acid (CLA) isomers, the natural rumen microbial metabolites, on lipopolysaccharide (LPS)-induced inflammation of ruminal epithelial cells (RECs) in vitro. The results showed that 100 μM trans-10,cis-12-CLA exerted higher anti-inflammatory effects than cis-9,trans-11-CLA by significantly downregulating the expression of genes related to inflammation, cell proliferation and migration in RECs upon LPS stimulation. Transcriptomic analyses further indicated that pretreatment with trans-10,cis-12-CLA, but not cis-9,trans-11-CLA, significantly suppressed the biological signals of GO terms’ response to LPS, the regulation of signal transduction and cytokine production and KEGG pathways NF-κB, chemokine, NOD-like receptor, Hippo, PI3K-Akt, TGF-β and Rap1 signaling in RECs upon LPS stimulation. Furthermore, pretreatment with trans-10,cis-12-CLA significantly reduced the expression of lipogenic genes and the biosynthesis of the unsaturated fatty acid pathway in RECs compared with the LPS group, however, cis-9,trans-11-CLA exhibited the opposite results. These results suggest the distinct isomer differences of CLA in the regulation of inflammatory responses and adipocytokine signaling in RECs and will provide important references for determining their target use in the future.
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Affiliation(s)
- Chunlei Yang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; (C.Y.); (B.Z.); (S.Y.)
| | - Binna Zhu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; (C.Y.); (B.Z.); (S.Y.)
| | - Shijie Ye
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; (C.Y.); (B.Z.); (S.Y.)
| | - Zhengwei Fu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; (C.Y.); (B.Z.); (S.Y.)
- Correspondence: (Z.F.); (J.L.)
| | - Jinjun Li
- Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
- Correspondence: (Z.F.); (J.L.)
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29
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Yang M, Zhang CY. G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment. World J Gastroenterol 2021; 27:677-691. [PMID: 33716447 PMCID: PMC7934005 DOI: 10.3748/wjg.v27.i8.677] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/24/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a broad-spectrum disease, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis, which can progress to cirrhosis and liver cancer. Abnormal hepatic lipid accumulation is the major manifestation of this disease, and lipotoxicity promotes NAFLD progression. In addition, intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins, resulting in progression of NAFLD to fibrosis and even cirrhosis. G protein-coupled receptors (GPCRs) have been shown to play essential roles in metabolic disorders, such as NAFLD and obesity, through their function as receptors for bile acids and free fatty acids. In addition, GPCRs link gut microbiota-mediated connections in a variety of diseases, such as intestinal diseases, hepatic steatosis, diabetes, and cardiovascular diseases. The latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty acids. GPCR agonists, including peptides and natural products like docosahexaenoic acid, have been applied to investigate their role in liver diseases. Therapies such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism syndrome. This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment. Overall, understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.
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Affiliation(s)
- Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Chun-Ye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65212, United States
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30
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Kent-Dennis C, Penner GB. Effects of a proinflammatory response on metabolic function of cultured, primary ruminal epithelial cells. J Dairy Sci 2020; 104:1002-1017. [PMID: 33131809 DOI: 10.3168/jds.2020-19092] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/11/2020] [Indexed: 12/14/2022]
Abstract
Inflammation of ruminal epithelium may occur during ruminal acidosis as a result of translocation and interaction of ruminal epithelial cells (REC) with molecules such as lipopolysaccharide (LPS). Such inflammation has been reported to alter cellular processes such as nutrient absorption, metabolic regulation, and energy substrate utilization in other cell types but has not been investigated for REC. The objectives of this study were to investigate the effects of LPS on metabolism of short-chain fatty acids by primary REC, as well as investigating the effects of media containing short-chain fatty acids on the proinflammatory response. Ruminal papillae from 9 yearling Speckle Park beef heifers were used to isolate and culture primary REC. Cells were grown in minimum essential medium (MEM) for 12 d before use and then reseeded in 24-well culture plates. The study was conducted as a 2 × 2 factorial, where cells were grown in unaltered MEM (REG) or medium containing 2 mM butyrate and 5 mM propionate (SCFA) with (50,000 EU/mL; +LPS) or without LPS (-LPS) for 24 h. Supernatant samples were collected for analysis of glucose and SCFA consumption. Cells were collected to determine the expression of mRNA for genes associated with inflammation (TNF, IL1B, CXCL2, CXCL8, PTGS2, and TLR4), purinergic signaling (P2RX7, ADORAB2, and CD73), nutrient transport [SLC16A1 (MCT1), SLC16A3 (MCT4), SLC5A8, and MCU], and cell metabolism [ACAT1, SLC2A1 (GLUT1), IGFBP3, and IGFBP5]. Protein expression of TLR4 and ketogenic enzymes (BDH1 and HMGCS1) were also analyzed using flow cytometry. Statistical analysis was conducted with the MIXED model of SAS version 9.4 (SAS Institute Inc., Cary, NC) with medium, LPS exposure, and medium × LPS interaction as fixed effects and animal within plate as a random effect. Cells tended to consume more glucose when exposed to LPS as opposed to no LPS exposure (31.8 vs. 28.7 ± 2.7), but consumption of propionate and butyrate was not influenced by LPS. Expression of TNF and IL1B was upregulated when exposed to LPS, and expression of CXCL2 and CXCL8 increased following LPS exposure with SCFA (medium × LPS). For cells exposed to LPS, we found a downregulation of ACAT1 and IGFBP5 and an upregulation of SLC2A1, SLC16A3, MCU, and IGFBP3. Medium with SCFA led to greater expression of MCU. SLC16A1 was upregulated in cells incubated with SCFA and without LPS compared with the other groups. Protein expression of ketogenic enzymes was not affected; however, BDH1 mean fluorescence intensity (MFI) expression tended to be less in cells exposed to LPS. These data are interpreted to indicate that when REC are exposed to LPS, they may increase glucose metabolism. Moreover, transport of solutes was affected by SCFA in the medium and by exposure to LPS. Overall, the results suggest that metabolic function of REC in vitro is altered by a proinflammatory response, which may lead to a greater glucose requirement.
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Affiliation(s)
- C Kent-Dennis
- Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5A8
| | - G B Penner
- Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5A8.
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31
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Establishment and identification of primary bovine omasal epithelial cells. In Vitro Cell Dev Biol Anim 2020; 56:495-499. [PMID: 32839903 DOI: 10.1007/s11626-020-00483-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 07/07/2020] [Indexed: 10/23/2022]
Abstract
The establishment and culture of bovine omasal epithelial cells (BOECs) in vitro is a valuable tool for the study of the physiological function, nutrient absorption, and transport mechanisms of the omasum in dairy cows. This paper proposes a method for the culture of primary BOECs. Trypsin digestion was used to subculture the BOECs, which were passaged for 20 generations in vitro, and showed typical epithelial-like characteristics and a cobblestone morphology. The primary BOECs had a fast growth phase (between days 4 and 5) and were validated by their slight β-galactosidase and visible cytokerat in 18 expression. In addition, RT-PCR results demonstrated that the monocarboxylate transporter 1 (MCT1), Na+/H+exchanger 1 (NHE1), and Na+/H+ exchanger 3 (NHE3) were expressed in the isolated primary BOECs. In conclusion, this primary BOEC isolation and culture model is a promising method for the study of nutrient absorption and regulation, as well as the immune regulation of epithelial cell transport in vitro.
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Auffret MD, Stewart RD, Dewhurst RJ, Duthie CA, Watson M, Roehe R. Identification of Microbial Genetic Capacities and Potential Mechanisms Within the Rumen Microbiome Explaining Differences in Beef Cattle Feed Efficiency. Front Microbiol 2020; 11:1229. [PMID: 32582125 PMCID: PMC7292206 DOI: 10.3389/fmicb.2020.01229] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 05/14/2020] [Indexed: 12/15/2022] Open
Abstract
In this study, Bos Taurus cattle offered one high concentrate diet (92% concentrate-8% straw) during two independent trials allowed us to classify 72 animals comprising of two cattle breeds as "Low" or "High" feed efficiency groups. Digesta samples were taken from individual beef cattle at the abattoir. After metagenomic sequencing, the rumen microbiome composition and genes were determined. Applying a targeted approach based on current biological evidence, 27 genes associated with host-microbiome interaction activities were selected. Partial least square analysis enabled the identification of the most significant genes and genera of feed efficiency (VIP > 0.8) across years of the trial and breeds when comparing all potential genes or genera together. As a result, limited number of genes explained about 40% of the variability in both feed efficiency indicators. Combining information from rumen metagenome-assembled genomes and partial least square analysis results, microbial genera carrying these genes were determined and indicated that a limited number of important genera impacting on feed efficiency. In addition, potential mechanisms explaining significant difference between Low and High feed efficiency animals were analyzed considering, based on the literature, their gastrointestinal location of action. High feed efficiency animals were associated with microbial species including several Eubacterium having the genetic capacity to form biofilm or releasing metabolites like butyrate or propionate known to provide a greater contribution to cattle energy requirements compared to acetate. Populations associated with fucose sensing or hemolysin production, both mechanisms specifically described in the lower gut by activating the immune system to compete with pathogenic colonizers, were also identified to affect feed efficiency using rumen microbiome information. Microbial mechanisms associated with low feed efficiency animals involved potential pathogens within Proteobacteria and Spirochaetales, releasing less energetic substrates (e.g., acetate) or producing sialic acid to avoid the host immune system. Therefore, this study focusing on genes known to be involved in host-microbiome interaction improved the identification of rumen microbial genetic capacities and potential mechanisms significantly impacting on feed efficiency in beef cattle fed high concentrate diet.
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Affiliation(s)
| | - Robert D. Stewart
- Division of Genetics and Genomics, The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom
| | | | | | - Mick Watson
- Division of Genetics and Genomics, The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom
- Edinburgh Genomics, The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom
| | - Rainer Roehe
- Scotland’s Rural College (SRUC), Edinburgh, United Kingdom
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Sfera A, Osorio C, Diaz EL, Maguire G, Cummings M. The Other Obesity Epidemic-Of Drugs and Bugs. Front Endocrinol (Lausanne) 2020; 11:488. [PMID: 32849279 PMCID: PMC7411001 DOI: 10.3389/fendo.2020.00488] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022] Open
Abstract
Chronic psychiatric patients with schizophrenia and related disorders are frequently treatment-resistant and may require higher doses of psychotropic drugs to remain stable. Prolonged exposure to these agents increases the risk of weight gain and cardiometabolic disorders, leading to poorer outcomes and higher medical cost. It is well-established that obesity has reached epidemic proportions throughout the world, however it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Psychotropic drugs have emerged as a major cause of weight gain, pointing to an urgent need for novel interventions to attenuate this unintended consequence. Recently, the gut microbial community has been linked to psychotropic drugs-induced obesity as these agents were found to possess antimicrobial properties and trigger intestinal dysbiosis, depleting Bacteroidetes phylum. Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the later alter the metabolism of the former. Here we review the role of gut bacterial community in psychotropic drugs metabolism and dysbiosis. We discuss potential biomarkers reflecting the status of Bacteroidetes phylum and take a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation, strategies that may lower obesity rates in chronic psychiatric patients.
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Affiliation(s)
- Adonis Sfera
- Psychiatry, Loma Linda University, Loma Linda, CA, United States
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
- *Correspondence: Adonis Sfera
| | - Carolina Osorio
- Department of Psychiatry, Loma Linda University, Loma Linda, CA, United States
| | - Eddie Lee Diaz
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
| | - Gerald Maguire
- Department of Psychiatry, University of California, Riverside, Riverside, CA, United States
| | - Michael Cummings
- Department of Psychiatry, Patton State Hospital, San Bernardino, CA, United States
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