AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.
BACKGROUND Phosphatidylinositol-3-kinases(PI3K)is a well-known route in inflammationrelated cancer.Recent discovery on PI3K-related genes revealed a potential variant that links ulcerative colitis(UC)and colorectal ca...BACKGROUND Phosphatidylinositol-3-kinases(PI3K)is a well-known route in inflammationrelated cancer.Recent discovery on PI3K-related genes revealed a potential variant that links ulcerative colitis(UC)and colorectal cancer(CRC)with colitisassociated cancer(CAC).PI3K/AKT pathway has been recommended as a potential additional therapeutic option for CRC due to its substantial role in modifying cellular processes.Buparlisib is a pan-class I PI3K inhibitor previously shown to reduce tumor growth.AIM To investigate the regulation of rs10889677 and the role of buparlisib in the PI3K signaling pathway in CAC pathogenesis.METHODS Genomic DNA from 32 colonic samples,including CAC(n=7),UC(n=10)and CRC(n=15),was sequenced for the rs10889677 mutation.The mutant and wildtype fragments were amplified and cloned in the pmirGLO vector.The luciferase activity of cloned vectors was assessed after transfection into the HT29 cell line.CAC mice were induced by a mixture of a single azoxymethane injection and three cycles of dextran sulphate sodium,then buparlisib was administered after 14 d.The excised colon was subjected to immunohistochemistry for Ki67 and Cleaved-caspase-3 markers and quantitative real-time polymerase chain reaction analysis for Pdk1 and Sgk2.RESULTS Luciferase activity decreased by 2.07-fold in the rs10889677 mutant,confirming the hypothesis that the variant disrupted miRNA binding sites,which led to an increase in IL23R expression and the activation of the PI3K signaling pathway.Furthermore,CAC-induced mice had a significantly higher disease activity index(P<0.05).Buparlisib treatment significantly decreased mean weight loss in CAC-induced mice(P<0.05),reduced the percentage of proliferating cells by 5%,and increased the number of apoptotic cells.The treatment also caused a downward trend of Pdk1 expression and significantly decreased Sgk2 expression.CONCLUSION Our findings suggested that the rs10889677 variant as a critical initiator of the PI3K signaling pathway,and buparlisib had the ability to prevent PI3K-non-AKT activation in the pathophysiology of CAC.展开更多
AIM:To investigate the utility of intestinal disaccharide analysis during esophagogastroduodenoscopy(EGD)in children,we performed a systematic review of studies examining disaccharide activity.METHODS:All full-length ...AIM:To investigate the utility of intestinal disaccharide analysis during esophagogastroduodenoscopy(EGD)in children,we performed a systematic review of studies examining disaccharide activity.METHODS:All full-length articles published in English during 1966-2014 were included if:(1)participants had small intestinal biopsy evaluation of disaccharide activity;(2)levels of lactase,sucrase,maltase or palatinase were reported;and(3)age of participants was under 18 years.RESULTS:Thirty articles examining 34753 disaccharide assays fulfilled the specific search,inclusion,and exclusion criteria.All of the studies were observational in design and 57%(17)were prospective.Sixteen studies were conducted in the United States and 9European studies were identified.The biggest study enrolled about 30,314 procedures and 13 studies investigated fewer than 50 procedures.Eleven studies examined Caucasian subjects,3 studies examined Asian subjects,and 6 examined African subjects.Only one Hispanic subject was included.In studies reporting disaccharide deficiency,the overall proportion of lactase deficiency was 39.2%,sucrase deficiency was9.0%,maltase deficiency was 12.6%and palatinase deficiency was 9.1%.The prevalence of duodenal inflammatory changes ranged from 6%to 24%for nonspecific histological lesions(e.g.,duodenitis).Sixteen studies examined the association of histologic findings with disaccharide activities,and 12 studies reported an inverse association between degree of histologic inflammation and disaccharide levels.CONCLUSION:We reviewed 30 studies including34753 biopsy specimens with disaccharide analysis from children undergoing EGD.Our findings advocate a large study is to further illuminate the importance of EGDwith disaccharide analysis in children.展开更多
The aim of this study is to compare ACE inhibitory,anti-diabetic and Anti-inflammatory activity of buffalo and camel milk using Lacticaseibacillus paracasei(M11)in combination with yeast Saccharomyces cerevisiae(WBS2A...The aim of this study is to compare ACE inhibitory,anti-diabetic and Anti-inflammatory activity of buffalo and camel milk using Lacticaseibacillus paracasei(M11)in combination with yeast Saccharomyces cerevisiae(WBS2A)and to release peptides with antihypertensive and anti-diabetic properties.Fermented buffalo and camel milk were considered for the evaluation of Angiotensin-converting enzyme(ACE)inhibitory and anti-diabetic activities at specific time intervals(12,24,36 and 48 h)at 37℃.For the growth condition optimization,proteolytic activity was evaluated with specific inoculation rates(1.5%,2.0%,and 2.5%)and at specific incubation periods(12,24,36,and 48 h).The highest peptides were produced at 2.5%inoculation rate and at 48 h of incubation in both buffalo and camel milk at 37℃.Further,camel and buffalo milk fermented with M11+WBS2A significantly lower the overproduction of TNF-α,IL-6,IL-1βand Nitric oxide(NO),that was induced by lipopolysaccharide(LPS)stimulation in RAW 267.4 cells.For protein purification,2D gel electrophoresis and SDS-PAGE were used.Camel and buffalo milk that had not been fermented displayed protein bands between 10 and 100 kDa and 10 and 75 kDa respectively,whereas all the fermented samples showed bands between 10 and 75 kDa.On SDS-PAGE,in permeates,there were no apparent protein bands.When fermented buffalo and camel milk were electrophoresed in 2D gel,a total of 26 and 25 protein spots were found.In 2D gel electrophoresis,protein spots had sizes between 10 and 37 kDa.In RP-HPLC,water-soluble extracts(WSEs)of ultra-filtered fractions were used to distinguish different fractions of a peptide.Peakview software was used to characterize the LC/MS results.Fourier transform-infrared spectroscopy(FTIR)was used to evaluate various functional groups of fermented milks.In molecular docking study,the peptide sequences identified from the fermented buffalo milk(FBM)and camel milk(FCM)were examined for their binding affinity against the binding sites of hPAM and hMGA.展开更多
The antioxidative,antimicrobial,and anti-inflammatory properties of fermented sheep milk with L.fermentum (KGL4),as well as the generation of antioxidative and antimicrobial peptides,are evaluated in the study.Antioxi...The antioxidative,antimicrobial,and anti-inflammatory properties of fermented sheep milk with L.fermentum (KGL4),as well as the generation of antioxidative and antimicrobial peptides,are evaluated in the study.Antioxidative and antibacterial activities in sheep milk fermented with KGL4 increased with incubation hours,along with varied antioxidative properties (ABTS assay:35.12%,hydroxyl free radical scavenging assay:29.12%,superoxide free radical scavenging activity:36.38%).Antimicrobial activity of fermented sheep milk against E.faecalis (19 mm),S.typhimurium (15.67 mm),B.cereus (14 mm),and E.coli (13 mm) was also observed.Furthermore,after 48 h,the KGL4 showed maximum proteolysis (10.40 mg/ml) at 2.5% rate of addition sheep milk.The antioxidative and antimicrobial activities of fermented sheep milk fractions (3 kDa and 10 kDa permeates and retentates) were also investigated.The highest ABTS activity (26.90%) was found in 10 kDa permeate,whereas the 3 kDa retentate had higher hydroxyl free radical scavenging activity (69.20%) and 3 kDa permeate showed maximum superoxide free radical scavenging activity (32.85%).The 10 kDa retentate had shown maximum antimicrobial activity against S.typhimurium (13.67 mm) and E.faecalis (17.00 mm).Proteins spotted on 2D gel electrophoresis of KGL4 were varied from 10 to 70 kDa.RP-LC/MS was used to identify 5 novel peptide sequences from 2-D gel spots.Searches in the BIOPEP database confirmed the antioxidative and antimicrobial effects of the novel fermented sheep milk peptides.Fermented sheep milk with KGL4 (SMKGL4) significantly reduced excessive TNF-α,IL-6,& IL-1β production in LPS-activated RAW 264.7 cells.展开更多
Whey protein concentrate-80(WPC-80)fermented with L.fermentum(KGL4)(37℃)and S.cerevisiae(WBS2A)(25℃)was tested for ACE-inhibitory and antioxidant activities over different periods(12,24,36 and 48 h).Proteolytic acti...Whey protein concentrate-80(WPC-80)fermented with L.fermentum(KGL4)(37℃)and S.cerevisiae(WBS2A)(25℃)was tested for ACE-inhibitory and antioxidant activities over different periods(12,24,36 and 48 h).Proteolytic activity(OPA method)was used to optimize the growth conditions(inoculation rate,i.e.at 1.5%,2.0%,and 2.5%and incubation time,i.e.12,24,36,and 48 h)for peptide production.Results indicated that the highest amount of peptides was obtained at 7.24 mg/mL for KGL4(37℃,48 h)and 8.59 mg/mL for WBS2A(25℃,48 h).The whey protein fermentate inhibited the LPS-induced NO production,while enhanced production concentrations of TNF-α,IL-6,and IL-1β.Subsequently,SDS-PAGE,as well as Two-Dimensional(2D)gel electrophoresis methods,were applied for protein purification using water-soluble extracts(WSEs)of WPC-80 fermented by a combination of L.fermentum and S.cerevisiae.On SDS-PAGE,protein bands were observed in the range of 10-55 kDa,whereas on the 2D page,protein spots were in the range of 10-70 kDa.All the 2D spots were analyzed using RPLC/MS.WSEs of 3 kDa and 10 kDa permeates were used in RP-HPLC to identify distinct peptide fractions.The data from LC/MS was also characterized by utilizing ProteinPilot software.Further,different functional groups were also analyzed using FTIR investigation.The research aims to isolate and characterize novel ACE-inhibitory and antioxidative peptides from fermented WPC-80 produced by Lactobacillus fermentum and S.cerevisiae.展开更多
基金Supported by Sigrid Juselius Foundationthe Finnish Pediatric Research Foundation
文摘AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.
基金The Fundamental Research Grant Scheme,Ministry of Higher Education,Malaysia,No.FRGS/1/2018/SKK06/UKM/02/4.
文摘BACKGROUND Phosphatidylinositol-3-kinases(PI3K)is a well-known route in inflammationrelated cancer.Recent discovery on PI3K-related genes revealed a potential variant that links ulcerative colitis(UC)and colorectal cancer(CRC)with colitisassociated cancer(CAC).PI3K/AKT pathway has been recommended as a potential additional therapeutic option for CRC due to its substantial role in modifying cellular processes.Buparlisib is a pan-class I PI3K inhibitor previously shown to reduce tumor growth.AIM To investigate the regulation of rs10889677 and the role of buparlisib in the PI3K signaling pathway in CAC pathogenesis.METHODS Genomic DNA from 32 colonic samples,including CAC(n=7),UC(n=10)and CRC(n=15),was sequenced for the rs10889677 mutation.The mutant and wildtype fragments were amplified and cloned in the pmirGLO vector.The luciferase activity of cloned vectors was assessed after transfection into the HT29 cell line.CAC mice were induced by a mixture of a single azoxymethane injection and three cycles of dextran sulphate sodium,then buparlisib was administered after 14 d.The excised colon was subjected to immunohistochemistry for Ki67 and Cleaved-caspase-3 markers and quantitative real-time polymerase chain reaction analysis for Pdk1 and Sgk2.RESULTS Luciferase activity decreased by 2.07-fold in the rs10889677 mutant,confirming the hypothesis that the variant disrupted miRNA binding sites,which led to an increase in IL23R expression and the activation of the PI3K signaling pathway.Furthermore,CAC-induced mice had a significantly higher disease activity index(P<0.05).Buparlisib treatment significantly decreased mean weight loss in CAC-induced mice(P<0.05),reduced the percentage of proliferating cells by 5%,and increased the number of apoptotic cells.The treatment also caused a downward trend of Pdk1 expression and significantly decreased Sgk2 expression.CONCLUSION Our findings suggested that the rs10889677 variant as a critical initiator of the PI3K signaling pathway,and buparlisib had the ability to prevent PI3K-non-AKT activation in the pathophysiology of CAC.
文摘AIM:To investigate the utility of intestinal disaccharide analysis during esophagogastroduodenoscopy(EGD)in children,we performed a systematic review of studies examining disaccharide activity.METHODS:All full-length articles published in English during 1966-2014 were included if:(1)participants had small intestinal biopsy evaluation of disaccharide activity;(2)levels of lactase,sucrase,maltase or palatinase were reported;and(3)age of participants was under 18 years.RESULTS:Thirty articles examining 34753 disaccharide assays fulfilled the specific search,inclusion,and exclusion criteria.All of the studies were observational in design and 57%(17)were prospective.Sixteen studies were conducted in the United States and 9European studies were identified.The biggest study enrolled about 30,314 procedures and 13 studies investigated fewer than 50 procedures.Eleven studies examined Caucasian subjects,3 studies examined Asian subjects,and 6 examined African subjects.Only one Hispanic subject was included.In studies reporting disaccharide deficiency,the overall proportion of lactase deficiency was 39.2%,sucrase deficiency was9.0%,maltase deficiency was 12.6%and palatinase deficiency was 9.1%.The prevalence of duodenal inflammatory changes ranged from 6%to 24%for nonspecific histological lesions(e.g.,duodenitis).Sixteen studies examined the association of histologic findings with disaccharide activities,and 12 studies reported an inverse association between degree of histologic inflammation and disaccharide levels.CONCLUSION:We reviewed 30 studies including34753 biopsy specimens with disaccharide analysis from children undergoing EGD.Our findings advocate a large study is to further illuminate the importance of EGDwith disaccharide analysis in children.
文摘The aim of this study is to compare ACE inhibitory,anti-diabetic and Anti-inflammatory activity of buffalo and camel milk using Lacticaseibacillus paracasei(M11)in combination with yeast Saccharomyces cerevisiae(WBS2A)and to release peptides with antihypertensive and anti-diabetic properties.Fermented buffalo and camel milk were considered for the evaluation of Angiotensin-converting enzyme(ACE)inhibitory and anti-diabetic activities at specific time intervals(12,24,36 and 48 h)at 37℃.For the growth condition optimization,proteolytic activity was evaluated with specific inoculation rates(1.5%,2.0%,and 2.5%)and at specific incubation periods(12,24,36,and 48 h).The highest peptides were produced at 2.5%inoculation rate and at 48 h of incubation in both buffalo and camel milk at 37℃.Further,camel and buffalo milk fermented with M11+WBS2A significantly lower the overproduction of TNF-α,IL-6,IL-1βand Nitric oxide(NO),that was induced by lipopolysaccharide(LPS)stimulation in RAW 267.4 cells.For protein purification,2D gel electrophoresis and SDS-PAGE were used.Camel and buffalo milk that had not been fermented displayed protein bands between 10 and 100 kDa and 10 and 75 kDa respectively,whereas all the fermented samples showed bands between 10 and 75 kDa.On SDS-PAGE,in permeates,there were no apparent protein bands.When fermented buffalo and camel milk were electrophoresed in 2D gel,a total of 26 and 25 protein spots were found.In 2D gel electrophoresis,protein spots had sizes between 10 and 37 kDa.In RP-HPLC,water-soluble extracts(WSEs)of ultra-filtered fractions were used to distinguish different fractions of a peptide.Peakview software was used to characterize the LC/MS results.Fourier transform-infrared spectroscopy(FTIR)was used to evaluate various functional groups of fermented milks.In molecular docking study,the peptide sequences identified from the fermented buffalo milk(FBM)and camel milk(FCM)were examined for their binding affinity against the binding sites of hPAM and hMGA.
文摘The antioxidative,antimicrobial,and anti-inflammatory properties of fermented sheep milk with L.fermentum (KGL4),as well as the generation of antioxidative and antimicrobial peptides,are evaluated in the study.Antioxidative and antibacterial activities in sheep milk fermented with KGL4 increased with incubation hours,along with varied antioxidative properties (ABTS assay:35.12%,hydroxyl free radical scavenging assay:29.12%,superoxide free radical scavenging activity:36.38%).Antimicrobial activity of fermented sheep milk against E.faecalis (19 mm),S.typhimurium (15.67 mm),B.cereus (14 mm),and E.coli (13 mm) was also observed.Furthermore,after 48 h,the KGL4 showed maximum proteolysis (10.40 mg/ml) at 2.5% rate of addition sheep milk.The antioxidative and antimicrobial activities of fermented sheep milk fractions (3 kDa and 10 kDa permeates and retentates) were also investigated.The highest ABTS activity (26.90%) was found in 10 kDa permeate,whereas the 3 kDa retentate had higher hydroxyl free radical scavenging activity (69.20%) and 3 kDa permeate showed maximum superoxide free radical scavenging activity (32.85%).The 10 kDa retentate had shown maximum antimicrobial activity against S.typhimurium (13.67 mm) and E.faecalis (17.00 mm).Proteins spotted on 2D gel electrophoresis of KGL4 were varied from 10 to 70 kDa.RP-LC/MS was used to identify 5 novel peptide sequences from 2-D gel spots.Searches in the BIOPEP database confirmed the antioxidative and antimicrobial effects of the novel fermented sheep milk peptides.Fermented sheep milk with KGL4 (SMKGL4) significantly reduced excessive TNF-α,IL-6,& IL-1β production in LPS-activated RAW 264.7 cells.
文摘Whey protein concentrate-80(WPC-80)fermented with L.fermentum(KGL4)(37℃)and S.cerevisiae(WBS2A)(25℃)was tested for ACE-inhibitory and antioxidant activities over different periods(12,24,36 and 48 h).Proteolytic activity(OPA method)was used to optimize the growth conditions(inoculation rate,i.e.at 1.5%,2.0%,and 2.5%and incubation time,i.e.12,24,36,and 48 h)for peptide production.Results indicated that the highest amount of peptides was obtained at 7.24 mg/mL for KGL4(37℃,48 h)and 8.59 mg/mL for WBS2A(25℃,48 h).The whey protein fermentate inhibited the LPS-induced NO production,while enhanced production concentrations of TNF-α,IL-6,and IL-1β.Subsequently,SDS-PAGE,as well as Two-Dimensional(2D)gel electrophoresis methods,were applied for protein purification using water-soluble extracts(WSEs)of WPC-80 fermented by a combination of L.fermentum and S.cerevisiae.On SDS-PAGE,protein bands were observed in the range of 10-55 kDa,whereas on the 2D page,protein spots were in the range of 10-70 kDa.All the 2D spots were analyzed using RPLC/MS.WSEs of 3 kDa and 10 kDa permeates were used in RP-HPLC to identify distinct peptide fractions.The data from LC/MS was also characterized by utilizing ProteinPilot software.Further,different functional groups were also analyzed using FTIR investigation.The research aims to isolate and characterize novel ACE-inhibitory and antioxidative peptides from fermented WPC-80 produced by Lactobacillus fermentum and S.cerevisiae.
