Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massiv...Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.展开更多
AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine rel...AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.展开更多
AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized doub...AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P【0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P 【0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.展开更多
The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regul...The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.展开更多
Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nucl...Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, harrier function and prevention of bacterial manslocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide, range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved展开更多
Poultry is widely produced and consumed meat globally.Its demand is expected to continue increasing to meet the animal protein requirement for ever-increasing human population.Thus,the challenge that poultry scientist...Poultry is widely produced and consumed meat globally.Its demand is expected to continue increasing to meet the animal protein requirement for ever-increasing human population.Thus,the challenge that poultry scientists and industry face are to produce sufficient amount of poultry meat in the most efficient way.In the past,using antibiotics to promote the growth of poultry and manage gut microbiota was a norm.However,due to concerns over potential fatalistic impacts on food animals and indirectly to humans,their use as feed additives are banned or regulated in several jurisdictions.In this changed context,several alternative strategies have been proposed with some success that mimics the functions of antibiotics as growth promoters and modulate gut microbiota for their beneficial roles.These include the use of probiotics,prebiotics,organic acids,and exogenous enzyme,among others.Gut microbiota and their metabolic products improve nutrient digestion,absorption,metabolism,and overall health and growth performance of poultry.This paper reviews the available information on the effect of feed additives used to modulate intestinal microbiota of poultry and their effects on overall health and growth performance.Understanding these functions and interactions will help to develop new dietary and managerial strategies that will ultimately lead to enhanced feed utilization and improved growth performance of poultry.This review will help future researchers and industry to identify alternative feed ingredients having properties like prebiotics,probiotics,organic acids,and exogenous enzymes.展开更多
Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy.Increased lipid uptake,storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth.Lipids constitute the ba...Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy.Increased lipid uptake,storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth.Lipids constitute the basic struc-ture of membranes and also function as signaling molecules and energy sources.Sterol regulatory element-binding proteins(SREBPs),a family of membrane-bound transcription factors in the endoplasmic reticulum,play a central role in the regulation of lipid metabolism.Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth.SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor,thus linking glucose metabolism and de novo lipid synthesis.Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy.This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy,and highlights potential molecu-lar targets and their inhibitors for cancer treatment.展开更多
The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulatingthe activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microb...The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulatingthe activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probioticstreated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutri展开更多
Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious eff...Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis, include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term, and selection for apoptosis resistance in the long term. These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.展开更多
Background: Two trials were performed to evaluate a partially defatted Hermetia illucens(HI) larvae meal as potential feed ingredient in rainbow trout(Oncorhynchus mykiss Walbaum) diets. In the first trial, 360 trout(...Background: Two trials were performed to evaluate a partially defatted Hermetia illucens(HI) larvae meal as potential feed ingredient in rainbow trout(Oncorhynchus mykiss Walbaum) diets. In the first trial, 360 trout(178.9 ± 9.8 g of mean initial body weight) were randomly divided into three experimental groups(4 tanks/treatment, 30 fish/tank). The fish were fed for 78 days with isonitrogenous, isolipidic and isoenergetic diets containing increasing levels of HI, on as fed basis: 0%(HI0, control diet), 25%(HI25) and 50%(HI50) of fish meal substitution, corresponding to dietary inclusion levels of 0, 20% and 40%. In the second trial, 36 trout(4 tanks/treatment, 3 fish/tank) were used to evaluate the in vivo apparent digestibility coefficients(ADC) of the same diets used in the first trial.Results: Survival, growth performance, condition factor, somatic indexes, and dorsal fillet physical quality parameters were not affected by diet. The highest dietary inclusion of HI larvae meal increased dry matter and ether extract contents of trout dorsal fillet. The use of HI larvae meal induced a decrease of valuable polyunsaturated fatty acids(PUFA) even if differences were only reported at the highest level of HI inclusion. The insect meal worsened the lipids health indexes of the same muscle. Dietary inclusion of insect meal did not alter the villus height of the fish. No differences were found among treatments in relation to ADC of ether extract and gross energy, while ADC of dry matter and crude protein were higher in HI25 if compared to HI50.Conclusions: The obtained results showed that a partially defatted HI larvae meal can be used as feed ingredient in trout diets up to 40% of inclusion level without impacting survival, growth performance, condition factor, somatic indexes, dorsal fillet physical quality parameters, and intestinal morphology of the fish. However, further investigations on specific feeding strategies and diet formulations are needed to limit the observed negative effects of the insect meal on the FA展开更多
The humic acids (HAs) isolated from the sediments of the various rivers,lakes,and reservoirs in China were studied using elemental analyzer,fourier transform infrared (FT-IR),and CP/MAS 13C nuclear magnetic resonance ...The humic acids (HAs) isolated from the sediments of the various rivers,lakes,and reservoirs in China were studied using elemental analyzer,fourier transform infrared (FT-IR),and CP/MAS 13C nuclear magnetic resonance (NMR) spectroscopy.The results showed that the HAs were characterized by some common chemical and physicochemical properties,but they also pose some differences in the C-containing functional groups.The C/N,C/H,O/C,and O/H ratios differ widely for the various HAs,showing that the elemental comp...展开更多
The phytochemical progress on Angelica sinensis(Oliv.) Diels over the past decades is summarized. Since 1970 s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromati...The phytochemical progress on Angelica sinensis(Oliv.) Diels over the past decades is summarized. Since 1970 s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides have been isolated or detected from the various parts of the title plant.展开更多
The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyze...The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.展开更多
A hydroponic experiment was carried out to study the effect of aluminum （Al） and cadmium （Cd） on Al and mineral nutrient contents in plants and Al-induced organic acid exudation in two barley varieties with differ...A hydroponic experiment was carried out to study the effect of aluminum （Al） and cadmium （Cd） on Al and mineral nutrient contents in plants and Al-induced organic acid exudation in two barley varieties with different Al tolerance. Al- sensitive cv. Shang 70-119 had significantly higher Al content and accumulation in plants than Al-tolerant cv. Gebeina, especially in roots, when subjected to low pH （4.0） and Al treatments （100 μmol L^-1 Al and 100 μmol L^-1 Al ＋1.0 μmol L^-1 Cd）. Cd addition increased Al content in plants exposed to Al stress. Both low pH and Al treatments caused marked reduction in Ca and Mg contents in all plant parts, P and K contents in the shoots and leaves, Fe, Zn and Mo contents in the leaves, Zn and B contents in the shoots, and Mn contents both in the roots and leaves. Moreover, changes in nutrient concentrations were greater in the plants exposed to both Al and Cd than in those exposed only to Al treatment. A dramatic enhancement of malate, citrate, and succinate was found in the plants exposed to 100 μmol L^-1 Al relative to the control, and the Al-tolerant cultivar had a considerable higher exudation of these organic acids than the Al-sensitive one, indicating that Al-induced enhancement of these organic acids is very likely to be associated with Al tolerance.展开更多
Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic c...Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.展开更多
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for trea...Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics （i.e., tissue plasminogen activator） and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies again st stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism（s） underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies （i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells） as it relates to cerebral ischemia.展开更多
This review article summarizes the efficacy, feasibility and potential mechanisms of the application of essential oils as antibiotic alternatives in swine production.Although there are numerous studies demonstrating t...This review article summarizes the efficacy, feasibility and potential mechanisms of the application of essential oils as antibiotic alternatives in swine production.Although there are numerous studies demonstrating that essential oils have several properties, such as antimicrobial, antioxidative and antiinflammatory effects, feed palatability enhancement and improvement in gut growth and health, there is still a need of further investigations to elucidate the mechanisms underlying their functions.In the past,the results has been inconsistent in both laboratory and field studies because of the varied product compositions, dosages, purities and growing stages and conditions of animals.The minimal inhibitory concentration(MIC) of essential oils needed for killing enteric pathogens may not ensure the optimal feed intake and the essential oils inclusion cost may be too high in swine production.With the lipophilic and volatile nature of essential oils, there is a challenge in effective delivery of essential oils within pig gut and this challenge can partially be resolved by microencapsulation and nanotechnology.The effects of essential oils on inflammation, oxidative stress, microbiome, gut chemosensing and bacterial quorum sensing(QS) have led to better production performance of animals fed essential oils in a number of studies.It has been demonstrated that essential oils have good potential as antibiotic alternatives in feeds for swine production.The combination of different essential oils and other compounds(synergistic effect) such as organic acids seems to be a promising approach to improve the efficacy and safety of essential oils in applications.High-throughput systems technologies have been developed recently,which will allow us to dissect the mechanisms underlying the functions of essential oils and facilitate the use of essential oils in swine production.展开更多
AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated fro...AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.展开更多
基金Supported by the National Natural Science Foundation of China,No.81760120 and No.81960128the Key Program of Science and Technology Department of Jiangxi Province,No.20171BBG70084 and No.20192ACBL20037.
文摘Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.
文摘AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
文摘AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P【0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P 【0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.
基金Supported by A Grant from Agenzia Italiana del Farmaco(AIFA) grant code FARM6FJ728
文摘The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.
基金supported by National Cancer Institute of United States (No.1R01-CA139158,to Wendong Huang)National Natural Science Foundation of China (Nos.81303186 and ZYX-NSFC-016)China Postdoctoral Science Foundation (No.2013M531202)
文摘Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, harrier function and prevention of bacterial manslocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide, range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved
基金Graduate student Sudhir Yadav was supported by USDA National Institute for Food and Agriculture,Hatch/Smith Lever Project HAW02030-H,managed by the College of Tropical Agriculture and Human Resources,University of Hawaii at Manoa,Honolulu,HI USA
文摘Poultry is widely produced and consumed meat globally.Its demand is expected to continue increasing to meet the animal protein requirement for ever-increasing human population.Thus,the challenge that poultry scientists and industry face are to produce sufficient amount of poultry meat in the most efficient way.In the past,using antibiotics to promote the growth of poultry and manage gut microbiota was a norm.However,due to concerns over potential fatalistic impacts on food animals and indirectly to humans,their use as feed additives are banned or regulated in several jurisdictions.In this changed context,several alternative strategies have been proposed with some success that mimics the functions of antibiotics as growth promoters and modulate gut microbiota for their beneficial roles.These include the use of probiotics,prebiotics,organic acids,and exogenous enzyme,among others.Gut microbiota and their metabolic products improve nutrient digestion,absorption,metabolism,and overall health and growth performance of poultry.This paper reviews the available information on the effect of feed additives used to modulate intestinal microbiota of poultry and their effects on overall health and growth performance.Understanding these functions and interactions will help to develop new dietary and managerial strategies that will ultimately lead to enhanced feed utilization and improved growth performance of poultry.This review will help future researchers and industry to identify alternative feed ingredients having properties like prebiotics,probiotics,organic acids,and exogenous enzymes.
基金supported by NIH Grant NS079701(DG)American Cancer Society Research Scholar Grant RSG-14-228-01-CSM(DG)+3 种基金OSUCCC Idea Grant(DG)an OSUCCC Translational Therapeutic Program seed grant(DG)a Pelotonia Postdoc Fellowship(CC)an OSU Department of Radiation-Oncology Basic Research seed Grant(CC).
文摘Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy.Increased lipid uptake,storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth.Lipids constitute the basic struc-ture of membranes and also function as signaling molecules and energy sources.Sterol regulatory element-binding proteins(SREBPs),a family of membrane-bound transcription factors in the endoplasmic reticulum,play a central role in the regulation of lipid metabolism.Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth.SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor,thus linking glucose metabolism and de novo lipid synthesis.Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy.This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy,and highlights potential molecu-lar targets and their inhibitors for cancer treatment.
文摘The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulatingthe activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probioticstreated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutri
基金Supported by Grants from the NIH (R21CA111513-01A1, 5 RO1 CA119087, and SPORE Grant 1 P50CA95060)grants from the Arizona Biomedical Research Commission (#0012 & #0803)by Biomedical Diagnostics & Research In., Tucson Arizona, and by a VA Merit Review Grant
文摘Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis, include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term, and selection for apoptosis resistance in the long term. These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.
基金Financial support for this work was provided by the University of Turin(ex 60%)grant(Es.fin.2015–2016)
文摘Background: Two trials were performed to evaluate a partially defatted Hermetia illucens(HI) larvae meal as potential feed ingredient in rainbow trout(Oncorhynchus mykiss Walbaum) diets. In the first trial, 360 trout(178.9 ± 9.8 g of mean initial body weight) were randomly divided into three experimental groups(4 tanks/treatment, 30 fish/tank). The fish were fed for 78 days with isonitrogenous, isolipidic and isoenergetic diets containing increasing levels of HI, on as fed basis: 0%(HI0, control diet), 25%(HI25) and 50%(HI50) of fish meal substitution, corresponding to dietary inclusion levels of 0, 20% and 40%. In the second trial, 36 trout(4 tanks/treatment, 3 fish/tank) were used to evaluate the in vivo apparent digestibility coefficients(ADC) of the same diets used in the first trial.Results: Survival, growth performance, condition factor, somatic indexes, and dorsal fillet physical quality parameters were not affected by diet. The highest dietary inclusion of HI larvae meal increased dry matter and ether extract contents of trout dorsal fillet. The use of HI larvae meal induced a decrease of valuable polyunsaturated fatty acids(PUFA) even if differences were only reported at the highest level of HI inclusion. The insect meal worsened the lipids health indexes of the same muscle. Dietary inclusion of insect meal did not alter the villus height of the fish. No differences were found among treatments in relation to ADC of ether extract and gross energy, while ADC of dry matter and crude protein were higher in HI25 if compared to HI50.Conclusions: The obtained results showed that a partially defatted HI larvae meal can be used as feed ingredient in trout diets up to 40% of inclusion level without impacting survival, growth performance, condition factor, somatic indexes, dorsal fillet physical quality parameters, and intestinal morphology of the fish. However, further investigations on specific feeding strategies and diet formulations are needed to limit the observed negative effects of the insect meal on the FA
基金the National Basic Research Program (973) of China (No.2004CB418502,2003CB415002)the National Natural Science Foundation of China (No.29977002).
文摘The humic acids (HAs) isolated from the sediments of the various rivers,lakes,and reservoirs in China were studied using elemental analyzer,fourier transform infrared (FT-IR),and CP/MAS 13C nuclear magnetic resonance (NMR) spectroscopy.The results showed that the HAs were characterized by some common chemical and physicochemical properties,but they also pose some differences in the C-containing functional groups.The C/N,C/H,O/C,and O/H ratios differ widely for the various HAs,showing that the elemental comp...
基金supported by the National Science & Technology Supporting Program for the 12th Five-year Plan(2011BAI05B02)the National Training Program of Innovation and Entrepreneurship for Undergraduates(201210731022)
文摘The phytochemical progress on Angelica sinensis(Oliv.) Diels over the past decades is summarized. Since 1970 s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides have been isolated or detected from the various parts of the title plant.
基金supported by Future Life Sciences International Ltd.(NSBJ01032014,http://ffsi.jpl)
文摘The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.
基金the Chinese Ministry of Science and Technology (China-Australian Special Link Research Program)the Grains Research and Development Corporation of Australia (No.UT-8).
文摘A hydroponic experiment was carried out to study the effect of aluminum （Al） and cadmium （Cd） on Al and mineral nutrient contents in plants and Al-induced organic acid exudation in two barley varieties with different Al tolerance. Al- sensitive cv. Shang 70-119 had significantly higher Al content and accumulation in plants than Al-tolerant cv. Gebeina, especially in roots, when subjected to low pH （4.0） and Al treatments （100 μmol L^-1 Al and 100 μmol L^-1 Al ＋1.0 μmol L^-1 Cd）. Cd addition increased Al content in plants exposed to Al stress. Both low pH and Al treatments caused marked reduction in Ca and Mg contents in all plant parts, P and K contents in the shoots and leaves, Fe, Zn and Mo contents in the leaves, Zn and B contents in the shoots, and Mn contents both in the roots and leaves. Moreover, changes in nutrient concentrations were greater in the plants exposed to both Al and Cd than in those exposed only to Al treatment. A dramatic enhancement of malate, citrate, and succinate was found in the plants exposed to 100 μmol L^-1 Al relative to the control, and the Al-tolerant cultivar had a considerable higher exudation of these organic acids than the Al-sensitive one, indicating that Al-induced enhancement of these organic acids is very likely to be associated with Al tolerance.
基金National Institutes of Health Grants,R01 CA 83650 and R01 CA 39225 to A.E.S.
文摘Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.
基金supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke grant 1R01NS096225-01A1the American Heart Association grants AHA-13SDG1395001413,AHA-17GRNT33660336,AHA-17POST33660174+1 种基金the Louisiana State University Grant in Aid research councilThe Malcolm Feist Cardiovascular Research Fellowship
文摘Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics （i.e., tissue plasminogen activator） and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies again st stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism（s） underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies （i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells） as it relates to cerebral ischemia.
基金supported by Natural Sciences and Engineering Council of Canada (NSERC) (CRDPJ 503580-16) Collaborative Research and Development Grants (C.Yang)the University of Manitoba Start-Up Grant (46561)+1 种基金Manitoba Pork Council (47370)Jefo Nutrition Inc (47369)
文摘This review article summarizes the efficacy, feasibility and potential mechanisms of the application of essential oils as antibiotic alternatives in swine production.Although there are numerous studies demonstrating that essential oils have several properties, such as antimicrobial, antioxidative and antiinflammatory effects, feed palatability enhancement and improvement in gut growth and health, there is still a need of further investigations to elucidate the mechanisms underlying their functions.In the past,the results has been inconsistent in both laboratory and field studies because of the varied product compositions, dosages, purities and growing stages and conditions of animals.The minimal inhibitory concentration(MIC) of essential oils needed for killing enteric pathogens may not ensure the optimal feed intake and the essential oils inclusion cost may be too high in swine production.With the lipophilic and volatile nature of essential oils, there is a challenge in effective delivery of essential oils within pig gut and this challenge can partially be resolved by microencapsulation and nanotechnology.The effects of essential oils on inflammation, oxidative stress, microbiome, gut chemosensing and bacterial quorum sensing(QS) have led to better production performance of animals fed essential oils in a number of studies.It has been demonstrated that essential oils have good potential as antibiotic alternatives in feeds for swine production.The combination of different essential oils and other compounds(synergistic effect) such as organic acids seems to be a promising approach to improve the efficacy and safety of essential oils in applications.High-throughput systems technologies have been developed recently,which will allow us to dissect the mechanisms underlying the functions of essential oils and facilitate the use of essential oils in swine production.
文摘AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.
