BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase prote...BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.展开更多
Pectinex XXL,a commercially prepared pectinase,was investigated for its potential application in the fruit juice industry.Polygalacturonic acid was used as the substrate for determining the enzymatic properties of Pec...Pectinex XXL,a commercially prepared pectinase,was investigated for its potential application in the fruit juice industry.Polygalacturonic acid was used as the substrate for determining the enzymatic properties of Pectinex XXL using the DNS method.According to the results,the optimal pH for Pectinex XXL activity was 4.5,and the enzyme was stable in the pH range of 3.0~4.5.The optimal pH and pH stability range are consistent with those of some tropical and subtropical fruits.The optimal temperature for Pectinex XXL activity was 60℃,and the enzyme remained stable after one hour in a water bath set at 40℃.Additionally,the enzymatic activity was not inhibited in the presence of 1 mmol/L of Na^(+),Mg^(2+),Ba^(2+),Co^(2+),Zn^(2+),and Fe^(2+),whereas it was slightly inhibited in the presence of 2 mmol/L of K^(+)and Fe^(2+)and partially inhibited in the presence of 1 and 2 mmol/L of Ca^(2+)and Mn^(2+),demonstrating its good stability in acids and excellent thermal catalytic performance.Based on the above experimental results,depectinization experiments were performed on plantain and cherry tomato juices using different amounts of Pectinex XXL.After one hour reaction with 16 U/mL of the enzyme,the yields of the plantain and cherry tomato juices were substantially increased by 119.03%and 15.97%,respectively,while their light transmittance was remarkably enhanced by 37.65%and 12.35%,respectively.Furthermore,the enzyme reduced the viscosity of the plantain and cherry tomato juices by 88.29%and 29.50%,respectively.The juice production experiments confirmed that this enzyme can significantly improve the yield and light transmittance of plantain juice,while effectively reducing its viscosity.These findings indicate the potential of Pectinex XXL in the industrial production of plantain juice.展开更多
Golden-flower fungus,the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea,is considered a potential probiotic fungus based on its anti-obesi...Golden-flower fungus,the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea,is considered a potential probiotic fungus based on its anti-obesity effect.However,the classification of golden-flower fungi is still controversial;the anti-obesity effect of golden-flower fungus polysaccharides remains unknown.In this study,we identify a golden-flower strain as Aspergillus cristatus based on morphological characteristics and multigene phylogeny analysis,which resolves the controversy of classification.Moreover,we find A.cristatus polysaccharides(ACPS)attenuate obesity in rats.ACPS modulate gut bacterial composition.in which Akkermansia,Akkermansia muciniphila,Bacteroides,Romboutsia,Blautia,and Desulfovibrio are considered the core microbes regulated by ACPS.ACPS increase fecal total short-chain fatty acid content and serum,hepatic,and fecal total bile acid content.Furthermore,ACPS-induced gut microbiota alteration plays a causal role in the protection from obesity,according to a fecal transplantation experiment.Thus,ACPS ameliorate obesity by regulating gut microbiota and gut microbiota-related metabolites.展开更多
AIM:To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus(A.fumigatus)keratitis in mice and the role of innate and adaptive immunity in it.METHODS:Mice models of A.fumigatus keratitis ...AIM:To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus(A.fumigatus)keratitis in mice and the role of innate and adaptive immunity in it.METHODS:Mice models of A.fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching.Subconjunctival injections of natamycin,wedelolactone,LOX-1 inhibitor(poly I)or Dectin-1 inhibitor(laminarin)were used to treat mice with A.fumigatus keratitis.Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε.We observed the corneal infection of mice under the slit lamp microscope and made a clinical score.The protein expression of CD3ε and interleukin-10(IL-10)was determined by Western blotting.RESULTS:With the disease progresses,the degree of corneal opacity and edema augmented.In the intrastromal injection models,CD3εprotein expression began to increase significantly on the 2^(nd) day.However,in the scraping epithelial method models,CD3ε only began to increase on the 3^(rd) day.After natamycin treatment,the degree of corneal inflammation in mice was significantly attenuated on the 3^(rd) day.After wedelolactone treatment,the severity of keratitis worsened.And the amount of CD3ε protein was also reduced,compared with the control group.By inhibiting LOX-1 and Dectin-1,there was no significant difference in CD3ε production compared with the control group.After inhibiting CD3ε,corneal ulcer area and clinical score increased,and IL-10 expression was downregulated.CONCLUSION:As a pan T cell marker,CD3ε participate in the adaptive immunity of A.fumigatus keratitis in mice.In our mice models,the corneas will enter the adaptive immune stage faster.By regulating IL-10,CD3ε exerts antiinflammatory and repairs effects in the adaptive immune stage.展开更多
We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroen...We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.展开更多
Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidat...Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.展开更多
对1株富产吲哚喹唑啉类生物碱(IQAs)的海绵共附生真菌Aspergillus giganteus MA 46-5的IQAs类成分进行了研究。根据IQAs的结构特征,在TLC、LC-MS和GNPS(global natural products social molecular networking)技术的共同指导下,从大米...对1株富产吲哚喹唑啉类生物碱(IQAs)的海绵共附生真菌Aspergillus giganteus MA 46-5的IQAs类成分进行了研究。根据IQAs的结构特征,在TLC、LC-MS和GNPS(global natural products social molecular networking)技术的共同指导下,从大米培养基的乙酸乙酯部位分离得到10个IQAs类生物碱。通过NMR、HR-ESI-MS、OR和CD等方法并结合文献比对鉴定其分别为:tryptoquivaline(1)、nortryptoquivaline(2)、deoxytryptoquivaline(3)、deoxynortryptoquivaline(4)、aspertoryadin C(5)、aspertoryadin G(6)、quinadoline A(7)、fiscalin E (8)、quinadoline B(9)和prelapatin B(10)。8和10为首次从Aspergillus属中得到,2、4~7为首次从Aspergillus giganteus中分离得到。展开更多
基金Supported by the Asociación de Celíacos y Sensibles al Gluten de Madrid,No.ACM2020)and Research Committee Argentine Society of Gastroenterology,No.2020.
文摘BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.
文摘Pectinex XXL,a commercially prepared pectinase,was investigated for its potential application in the fruit juice industry.Polygalacturonic acid was used as the substrate for determining the enzymatic properties of Pectinex XXL using the DNS method.According to the results,the optimal pH for Pectinex XXL activity was 4.5,and the enzyme was stable in the pH range of 3.0~4.5.The optimal pH and pH stability range are consistent with those of some tropical and subtropical fruits.The optimal temperature for Pectinex XXL activity was 60℃,and the enzyme remained stable after one hour in a water bath set at 40℃.Additionally,the enzymatic activity was not inhibited in the presence of 1 mmol/L of Na^(+),Mg^(2+),Ba^(2+),Co^(2+),Zn^(2+),and Fe^(2+),whereas it was slightly inhibited in the presence of 2 mmol/L of K^(+)and Fe^(2+)and partially inhibited in the presence of 1 and 2 mmol/L of Ca^(2+)and Mn^(2+),demonstrating its good stability in acids and excellent thermal catalytic performance.Based on the above experimental results,depectinization experiments were performed on plantain and cherry tomato juices using different amounts of Pectinex XXL.After one hour reaction with 16 U/mL of the enzyme,the yields of the plantain and cherry tomato juices were substantially increased by 119.03%and 15.97%,respectively,while their light transmittance was remarkably enhanced by 37.65%and 12.35%,respectively.Furthermore,the enzyme reduced the viscosity of the plantain and cherry tomato juices by 88.29%and 29.50%,respectively.The juice production experiments confirmed that this enzyme can significantly improve the yield and light transmittance of plantain juice,while effectively reducing its viscosity.These findings indicate the potential of Pectinex XXL in the industrial production of plantain juice.
基金financially supported by Natural Science Foundation of China (32002095 and 32172217)Major Project of Science and Technology of Guangxi Zhuang Autonomous Region (AA20302018)+4 种基金Key Research and Development Program of Hunan Province (2020WK2017)Hunan“Three Top”Innovative Talents Project (2022RC1142)Natural Science Foundation of Hunan Province for Outstanding Young Scholars (2022JJ20028)Training Program for Excellent Young Innovators of Changsha (kq2107015)Scientific Research Fund of the Hunan Provincial Education Department (20A241)。
文摘Golden-flower fungus,the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea,is considered a potential probiotic fungus based on its anti-obesity effect.However,the classification of golden-flower fungi is still controversial;the anti-obesity effect of golden-flower fungus polysaccharides remains unknown.In this study,we identify a golden-flower strain as Aspergillus cristatus based on morphological characteristics and multigene phylogeny analysis,which resolves the controversy of classification.Moreover,we find A.cristatus polysaccharides(ACPS)attenuate obesity in rats.ACPS modulate gut bacterial composition.in which Akkermansia,Akkermansia muciniphila,Bacteroides,Romboutsia,Blautia,and Desulfovibrio are considered the core microbes regulated by ACPS.ACPS increase fecal total short-chain fatty acid content and serum,hepatic,and fecal total bile acid content.Furthermore,ACPS-induced gut microbiota alteration plays a causal role in the protection from obesity,according to a fecal transplantation experiment.Thus,ACPS ameliorate obesity by regulating gut microbiota and gut microbiota-related metabolites.
基金Supported by the National Natural Science Foundation of China(No.82171019)the Natural Science Foundation of Shandong Province(No.ZR2021MH368)+1 种基金Traditional Chinese Medicine Research Project of Qingdao(No.2020-zyy055)Shandong Qingdao Outstanding Health Professional Development Fund.
文摘AIM:To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus(A.fumigatus)keratitis in mice and the role of innate and adaptive immunity in it.METHODS:Mice models of A.fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching.Subconjunctival injections of natamycin,wedelolactone,LOX-1 inhibitor(poly I)or Dectin-1 inhibitor(laminarin)were used to treat mice with A.fumigatus keratitis.Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε.We observed the corneal infection of mice under the slit lamp microscope and made a clinical score.The protein expression of CD3ε and interleukin-10(IL-10)was determined by Western blotting.RESULTS:With the disease progresses,the degree of corneal opacity and edema augmented.In the intrastromal injection models,CD3εprotein expression began to increase significantly on the 2^(nd) day.However,in the scraping epithelial method models,CD3ε only began to increase on the 3^(rd) day.After natamycin treatment,the degree of corneal inflammation in mice was significantly attenuated on the 3^(rd) day.After wedelolactone treatment,the severity of keratitis worsened.And the amount of CD3ε protein was also reduced,compared with the control group.By inhibiting LOX-1 and Dectin-1,there was no significant difference in CD3ε production compared with the control group.After inhibiting CD3ε,corneal ulcer area and clinical score increased,and IL-10 expression was downregulated.CONCLUSION:As a pan T cell marker,CD3ε participate in the adaptive immunity of A.fumigatus keratitis in mice.In our mice models,the corneas will enter the adaptive immune stage faster.By regulating IL-10,CD3ε exerts antiinflammatory and repairs effects in the adaptive immune stage.
文摘We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.
基金European Sequencing and Genotyping Institutes(ESGI),Grant/Award Number:075491/Z/04,085906/Z/08/Z and 090532/Z/09/ZTel-Aviv University(TAU)。
文摘Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.
基金the National Science-Technology Supporting Project for the 11th Five-Year Plan (Nos. 2006BAD27B09-6 and 2007BAK36B03)the Key Technology R&D Program of Guangdong Province (Nos. 2007A010900001 and 2008A010900001)
