AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or ...AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.展开更多
The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probioti...The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms “probiotics' and 'gene expression' combined with “intestines', 'liver', 'enterocytes', 'antigen-presenting cells', 'dendritic cells', 'immune system', and 'inflammation'. Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and interleukins and lead mainly to an anti-inflammatory response in cultured enterocytes. In addition, the interaction of commensal bacteria and probiotics with the surface of antigen-presenting cells in vitro results in the downregulation of pro-inflammatory genes that are linked to inflammatory signaling pathways, whereas other anti-inflammatory genes are upregulated. The effects of probiotics have been extensively investigated in animal models ranging from fish to mice, rats and piglets. These bacteria induce a tolerogenic and hyporesponsive immune response in which many genes that are related to the immune system, in particular those genes expressing anti-inflammatory cytokines, are upregulated. By contrast, information related to gene expression in human intestinal cells mediated by the action of probiotics is scarce. There is a need for further clinical studies that evaluate the mechanism of action of probiotics both in healthy humans and in patients with chronic diseases. These types of clinical studies are necessary for addressing the influence of these microorganisms in gene expression for different pathways, particularly those that are associated with the immune response, and to better understand the role that probiotics might have in the prevention and treatment of disease.展开更多
Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bo...Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bowel disease (IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease (with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy (whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor (TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity.展开更多
OBJECTIVE Na+/K+-ATPase(NKA)is large membrane protein expressed uni⁃versally which is indispensable for the mainte⁃nance of ionic gradient as well as neuronal excit⁃ability.The role of NKA in inflammatory regula⁃tion ...OBJECTIVE Na+/K+-ATPase(NKA)is large membrane protein expressed uni⁃versally which is indispensable for the mainte⁃nance of ionic gradient as well as neuronal excit⁃ability.The role of NKA in inflammatory regula⁃tion is still unclear.Inflammatory responses are initiated upon the activation of inflammasomes.In order to investigate the crosslink between NKA and inflammasome,NKAα1 knockout(KO)N2a cells were generated using CRISPR/Cas9 system.METHODS AND RESULTS qPCR results showed that NLRP1 and NLRP3 were upregulated in response to NKAα1 loss while both NLRC4 and AIM2 remained unaffected.Meanwhile,consistent with the change in NLRP1 and NLRP3,both the mRNA level of ASC and IL-1βwere significantly increased in NKAα1 KO cells.These data indicated that NKAα1 interfer⁃ence might influence the level of NLRP1 and NLRP3 inflammasomes in neuronal cells.Further evidence indicating the potential link between NKA and inflammasome pathway were provided using cytokine array assay where all the differen⁃tiated protein detected were closely linked to NLRP1 and NLRP3.To confirm this effect,we also observed the transcriptional levels of inflam⁃masome proteins in the brain cortex from both NKAα1+/+and NKAα1+/-mice.In line with the observation gained in NKAα1 KO cells,the mRNA level of NLRP1,NLRP3 and IL-1βwere significantly upregulated in NKAα1+/-mice brain.Interestingly,in the primary cultured astrocytes,treatment with LPS/ATP significantly reduced the mRNA and protein levels of NKAα1 expression.These data imply that a negative regulation loop between NKAα1 and inflammation may exist in the central nervous system.Since neuroinflam⁃matory mechanism is currently considered the most potential of interventions to target anxiety,we therefore perform behavioural experiments to investigate the role of NKAα1 in anxiety.Chronic restraint stress(CRS)for 10 d significantly reduced the time and frequency of entering the open arm and prolonged the retention time in the closed arm in the elevated plus-maze test.In the open field test,CRS also reduced both duration and frequency of entering into the central region.Although NKAα1 loss itself did not alter the behaviour performance in the normal condition,it exacerbated CRS-induced above behaviour abnormalities.CONCLUSION NKAα1 is regulat⁃ed upon inflammatory challenger and may be a novel target to treat anxiety.展开更多
Objective:To investigate the golden-time-awareness of and the necessary actions in response to acute myocardial infarction among the general public.Methods:This study was conducted with the use of a descriptive resear...Objective:To investigate the golden-time-awareness of and the necessary actions in response to acute myocardial infarction among the general public.Methods:This study was conducted with the use of a descriptive research design and convenience sampling.A sample of 800 subjects,using self-structured knowledge questionnaires,was selected for data collection and analysis.The study was conducted at Dr.M.G.R.Educational and Research Institute,India,from February to November 2022.Awareness of myocardial infarction symptoms and intervention timeline(the golden time)was investigated.A multivariate logistic regression analysis was performed to identify the demographic factors affecting the recognition of the golden time of acute myocardial infarction.Results:A total of 800 subjects were included.Among the subjects,367(45.8%)were male,433(54.2%)were female,and 443(55.3%)participants failed to recognize the golden time.Our multivariate logistic regression analysis showed that people with a bachelor’s degree(OR=0.41,95%CI:0.23-0.74,P=0.03)and a high school level diploma(OR=0.55,95%CI:0.31-0.97,P=0.03)are more likely to know about myocardial infarction(golden time)than illiterate people.Additionally,people who are employed(OR=0.59,95%CI:0.41-0.85,P=0.05)are more likely to know about myocardial infarction(golden time)than those who are not.Conclusions:The majority of people in the awareness group realize that taking myocardial infarction patients to the hospital would be the best course of action.The unawareness of the ideal treatment window for myocardial infarction may cause a delay in seeking medical attention,which can lead to an increase in mortality and morbidity.展开更多
Objective: In this study, we compared the biochemical markers of imminent abortion, missed abortion, and healthy pregnant women in the first trimester to see if there were any differences. Materials and Methods: The s...Objective: In this study, we compared the biochemical markers of imminent abortion, missed abortion, and healthy pregnant women in the first trimester to see if there were any differences. Materials and Methods: The study method is prospective. Pregnant women who applied to the obstetrics clinic of Istanbul Training and Research Hospital between 01.04.22 and 31.10.22 were diagnosed with abortion imminens or missed abortion between 6 weeks and 12 weeks or had normal pregnancy follow-up, had no chronic diseases, and did not take magnesium and calcium supplements were included in the study. 20 pregnant women with missed abortion, 20 pregnant women with abortion imminens diagnosis and 20 normal pregnant women who met the criteria were included in the study. Magnesium (Mg), calcium (Ca), copper (Cu), zinc (Zn) and hemogram (CBC) levels were checked in pregnant women included in the study. Results: The Mg, Cu, Zn, and CBC values of the study participants’ women did not differ in a statistically significant way. When compared to pregnant women who had a normal pregnancy process, the difference in Ca value was found to be statistically substantially smaller in pregnant women who were diagnosed with abortion imminens and missed abortion. The findings of our study suggest that serum Ca levels be measured prior to conception or at the initial visit. Conclusion: Serum Ca levels were found to be significantly lower in the missed abortion group than in the abortus imminens and normal pregnant groups in our study (p 0.05).展开更多
基金Supported by The Natural Sciences and Engineering Research Council of Canada,the Broad Foundation,the Canadian Institutes of Health Research and The Alberta Livestock and Meat Agency
文摘AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.
文摘The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms “probiotics' and 'gene expression' combined with “intestines', 'liver', 'enterocytes', 'antigen-presenting cells', 'dendritic cells', 'immune system', and 'inflammation'. Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and interleukins and lead mainly to an anti-inflammatory response in cultured enterocytes. In addition, the interaction of commensal bacteria and probiotics with the surface of antigen-presenting cells in vitro results in the downregulation of pro-inflammatory genes that are linked to inflammatory signaling pathways, whereas other anti-inflammatory genes are upregulated. The effects of probiotics have been extensively investigated in animal models ranging from fish to mice, rats and piglets. These bacteria induce a tolerogenic and hyporesponsive immune response in which many genes that are related to the immune system, in particular those genes expressing anti-inflammatory cytokines, are upregulated. By contrast, information related to gene expression in human intestinal cells mediated by the action of probiotics is scarce. There is a need for further clinical studies that evaluate the mechanism of action of probiotics both in healthy humans and in patients with chronic diseases. These types of clinical studies are necessary for addressing the influence of these microorganisms in gene expression for different pathways, particularly those that are associated with the immune response, and to better understand the role that probiotics might have in the prevention and treatment of disease.
文摘Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bowel disease (IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease (with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy (whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor (TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity.
文摘OBJECTIVE Na+/K+-ATPase(NKA)is large membrane protein expressed uni⁃versally which is indispensable for the mainte⁃nance of ionic gradient as well as neuronal excit⁃ability.The role of NKA in inflammatory regula⁃tion is still unclear.Inflammatory responses are initiated upon the activation of inflammasomes.In order to investigate the crosslink between NKA and inflammasome,NKAα1 knockout(KO)N2a cells were generated using CRISPR/Cas9 system.METHODS AND RESULTS qPCR results showed that NLRP1 and NLRP3 were upregulated in response to NKAα1 loss while both NLRC4 and AIM2 remained unaffected.Meanwhile,consistent with the change in NLRP1 and NLRP3,both the mRNA level of ASC and IL-1βwere significantly increased in NKAα1 KO cells.These data indicated that NKAα1 interfer⁃ence might influence the level of NLRP1 and NLRP3 inflammasomes in neuronal cells.Further evidence indicating the potential link between NKA and inflammasome pathway were provided using cytokine array assay where all the differen⁃tiated protein detected were closely linked to NLRP1 and NLRP3.To confirm this effect,we also observed the transcriptional levels of inflam⁃masome proteins in the brain cortex from both NKAα1+/+and NKAα1+/-mice.In line with the observation gained in NKAα1 KO cells,the mRNA level of NLRP1,NLRP3 and IL-1βwere significantly upregulated in NKAα1+/-mice brain.Interestingly,in the primary cultured astrocytes,treatment with LPS/ATP significantly reduced the mRNA and protein levels of NKAα1 expression.These data imply that a negative regulation loop between NKAα1 and inflammation may exist in the central nervous system.Since neuroinflam⁃matory mechanism is currently considered the most potential of interventions to target anxiety,we therefore perform behavioural experiments to investigate the role of NKAα1 in anxiety.Chronic restraint stress(CRS)for 10 d significantly reduced the time and frequency of entering the open arm and prolonged the retention time in the closed arm in the elevated plus-maze test.In the open field test,CRS also reduced both duration and frequency of entering into the central region.Although NKAα1 loss itself did not alter the behaviour performance in the normal condition,it exacerbated CRS-induced above behaviour abnormalities.CONCLUSION NKAα1 is regulat⁃ed upon inflammatory challenger and may be a novel target to treat anxiety.
文摘Objective:To investigate the golden-time-awareness of and the necessary actions in response to acute myocardial infarction among the general public.Methods:This study was conducted with the use of a descriptive research design and convenience sampling.A sample of 800 subjects,using self-structured knowledge questionnaires,was selected for data collection and analysis.The study was conducted at Dr.M.G.R.Educational and Research Institute,India,from February to November 2022.Awareness of myocardial infarction symptoms and intervention timeline(the golden time)was investigated.A multivariate logistic regression analysis was performed to identify the demographic factors affecting the recognition of the golden time of acute myocardial infarction.Results:A total of 800 subjects were included.Among the subjects,367(45.8%)were male,433(54.2%)were female,and 443(55.3%)participants failed to recognize the golden time.Our multivariate logistic regression analysis showed that people with a bachelor’s degree(OR=0.41,95%CI:0.23-0.74,P=0.03)and a high school level diploma(OR=0.55,95%CI:0.31-0.97,P=0.03)are more likely to know about myocardial infarction(golden time)than illiterate people.Additionally,people who are employed(OR=0.59,95%CI:0.41-0.85,P=0.05)are more likely to know about myocardial infarction(golden time)than those who are not.Conclusions:The majority of people in the awareness group realize that taking myocardial infarction patients to the hospital would be the best course of action.The unawareness of the ideal treatment window for myocardial infarction may cause a delay in seeking medical attention,which can lead to an increase in mortality and morbidity.
文摘Objective: In this study, we compared the biochemical markers of imminent abortion, missed abortion, and healthy pregnant women in the first trimester to see if there were any differences. Materials and Methods: The study method is prospective. Pregnant women who applied to the obstetrics clinic of Istanbul Training and Research Hospital between 01.04.22 and 31.10.22 were diagnosed with abortion imminens or missed abortion between 6 weeks and 12 weeks or had normal pregnancy follow-up, had no chronic diseases, and did not take magnesium and calcium supplements were included in the study. 20 pregnant women with missed abortion, 20 pregnant women with abortion imminens diagnosis and 20 normal pregnant women who met the criteria were included in the study. Magnesium (Mg), calcium (Ca), copper (Cu), zinc (Zn) and hemogram (CBC) levels were checked in pregnant women included in the study. Results: The Mg, Cu, Zn, and CBC values of the study participants’ women did not differ in a statistically significant way. When compared to pregnant women who had a normal pregnancy process, the difference in Ca value was found to be statistically substantially smaller in pregnant women who were diagnosed with abortion imminens and missed abortion. The findings of our study suggest that serum Ca levels be measured prior to conception or at the initial visit. Conclusion: Serum Ca levels were found to be significantly lower in the missed abortion group than in the abortus imminens and normal pregnant groups in our study (p 0.05).
