The bone extracellular matrix(ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of noncollagenous proteins. Some of these proteins are key to the regulation of bone formation and reg...The bone extracellular matrix(ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of noncollagenous proteins. Some of these proteins are key to the regulation of bone formation and regeneration via signaling pathways,and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix(ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database(available at https://phylobone.com) includes 255proteins potentially expressed in the bone extracellular matrix(ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of(biological) evolution,and will substantially contribute to the identification of molecular mechanisms and drug targets.展开更多
Irritable bowel syndrome(IBS)is a common clinical label for medically unexplained gastrointestinal symptoms,recently described as a disturbance of the microbiota-gut-brain axis.Despite decades of research,the pathophy...Irritable bowel syndrome(IBS)is a common clinical label for medically unexplained gastrointestinal symptoms,recently described as a disturbance of the microbiota-gut-brain axis.Despite decades of research,the pathophysiology of this highly heterogeneous disorder remains elusive.However,a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture.Are we getting any closer to understanding IBS’etiology,or are we drowning in unspecific,conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing?In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota,clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation,neuroimaging and methods in microbiota analyses,and current and future challenges with big data analysis in IBS.展开更多
Background: The EU ban on antimicrobial growth promoters (AGP) has initiated a search for non-antibiotic alternatives. It has been demonstrated that certain antibiotics and non-antibiotic alternatives enhance growth b...Background: The EU ban on antimicrobial growth promoters (AGP) has initiated a search for non-antibiotic alternatives. It has been demonstrated that certain antibiotics and non-antibiotic alternatives enhance growth by inhibiting inflammatory cells, i.e. neutrophils and macrophages in the intestine. There is very little information on the effect of anti-inflammatory compounds on intestinal epithelial cells, which are known to play an important role in intestinal inflammatory responses. In order to establish this, a porcine intestinal epithelial cell line (IPEC J2) was incubated with an adherent enterotoxigenic E. coli (ETEC) to stimulate inflammation, using a non-pathogenic non-adherent E. coli (EC) as a control. The influence of the presence of the anti-inflammatory compounds Macleaya cordata extract (MCE) and acetylsalicylic acid (ASA) on inflammatory transcriptional responses was studied. Results: ETEC induced a strong inflammatory response as was most evident from the expression of IL-1β, IL-8 and TNF-α, whereas EC induced IL-1βonly. Co-incubation with MCE and ASA significantly reduced the responses of the pro-inflammatory cytokines, similarly for IL-1βand TNF-α, but ASA was more effective than MCE in reducing the IL8 response. Conclusions: The present results suggest that the in vivo anti-inflammatory growth promoting effects of AGP and effective alternatives to AGP such as MCE and ASA are not restricted to inflammatory cells and also involve the more abundant enterocytes. This suggests a major role for epithelial cells in growth promotion livestock, and it further supports the notion that effective alternatives to AGP should have anti-inflammatory activity.展开更多
基金supported by continuation funds from the Turku Collegium for Science,Medicine and Technologythe Japan Society for the Promotion of Science (#23K08670)+1 种基金the Sigrid Jusélius Foundation (#230131)MF-R internship at the University of Turku was funded by the Erasmus+program。
文摘The bone extracellular matrix(ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of noncollagenous proteins. Some of these proteins are key to the regulation of bone formation and regeneration via signaling pathways,and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix(ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database(available at https://phylobone.com) includes 255proteins potentially expressed in the bone extracellular matrix(ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of(biological) evolution,and will substantially contribute to the identification of molecular mechanisms and drug targets.
基金Supported by the Spanish Ministry of Science and Innovation(MICINN,Spain),No.AGL2017-88801-P(to Sanz Y)the Miguel Server grant from the Spanish"Carlos III"Health Institute(ISCIII),No.CP19/00132(to Benitez-Paez A)+2 种基金The Norwegian Research Council(Funding Postdoc Position for Bharath Halandur Nagaraja),No.FRIMEDBIO276010and Helse Vest’s Research Funding,No.HV912243and ERC H2020-MSCA-IF-2019,No.895219(to Haleem N).
文摘Irritable bowel syndrome(IBS)is a common clinical label for medically unexplained gastrointestinal symptoms,recently described as a disturbance of the microbiota-gut-brain axis.Despite decades of research,the pathophysiology of this highly heterogeneous disorder remains elusive.However,a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture.Are we getting any closer to understanding IBS’etiology,or are we drowning in unspecific,conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing?In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota,clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation,neuroimaging and methods in microbiota analyses,and current and future challenges with big data analysis in IBS.
文摘Background: The EU ban on antimicrobial growth promoters (AGP) has initiated a search for non-antibiotic alternatives. It has been demonstrated that certain antibiotics and non-antibiotic alternatives enhance growth by inhibiting inflammatory cells, i.e. neutrophils and macrophages in the intestine. There is very little information on the effect of anti-inflammatory compounds on intestinal epithelial cells, which are known to play an important role in intestinal inflammatory responses. In order to establish this, a porcine intestinal epithelial cell line (IPEC J2) was incubated with an adherent enterotoxigenic E. coli (ETEC) to stimulate inflammation, using a non-pathogenic non-adherent E. coli (EC) as a control. The influence of the presence of the anti-inflammatory compounds Macleaya cordata extract (MCE) and acetylsalicylic acid (ASA) on inflammatory transcriptional responses was studied. Results: ETEC induced a strong inflammatory response as was most evident from the expression of IL-1β, IL-8 and TNF-α, whereas EC induced IL-1βonly. Co-incubation with MCE and ASA significantly reduced the responses of the pro-inflammatory cytokines, similarly for IL-1βand TNF-α, but ASA was more effective than MCE in reducing the IL8 response. Conclusions: The present results suggest that the in vivo anti-inflammatory growth promoting effects of AGP and effective alternatives to AGP such as MCE and ASA are not restricted to inflammatory cells and also involve the more abundant enterocytes. This suggests a major role for epithelial cells in growth promotion livestock, and it further supports the notion that effective alternatives to AGP should have anti-inflammatory activity.