Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating a...Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.展开更多
This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions o...This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.Modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.展开更多
Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed t...Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.展开更多
背景:如何修复骨缺损一直以来是临床难题,中药有效成分在骨修复方面具有良好的生物活性与治疗效果,将中药有效成分与组织工程材料相结合在骨修复领域具有广阔的前景。不同中药有效成分与支架的组合在作用关系方面具有相似之处。目的:搜...背景:如何修复骨缺损一直以来是临床难题,中药有效成分在骨修复方面具有良好的生物活性与治疗效果,将中药有效成分与组织工程材料相结合在骨修复领域具有广阔的前景。不同中药有效成分与支架的组合在作用关系方面具有相似之处。目的:搜集常见的中药有效成分与支架材料组合的案例,基于七情配伍的启发将组织工程支架与中药有效成分类比为产生配伍关系的两类中药,以二者的作用关系为纲进行归纳总结。方法:检索1998年1月至2024年1月Pub Med和中国知网数据库中发表的相关文献,英文检索词:“traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold”,中文检索词:“中药,中药有效成分,中药单体,骨组织工程,骨组织工程支架,支架,组织工程,骨缺损,骨修复”,最终纳入88篇文献进行综述分析。结果与结论:(1)组织工程支架材料与中药有效成分各自均在骨修复领域有广泛的运用,二者在成骨方面优势明显但仍有许多缺陷,许多研究致力于将二者制备成复合材料,希望通过二者间的相互作用发挥减毒增效作用。(2)一些药物与材料在成骨、抗菌、促血管生成方面能互相促进,增强原有的效果,受到传统方剂配伍观念的启发,文章将其归纳为“相须”关系,并举实例佐证。(3)一些药物能提高材料的强度,而某些材料能对负载于其上的药物实现缓释控释效果、增加载药量与稳定性,或是进行靶向递送,文章将这种单方面的提升效果归纳为“相使”关系。(4)一些中药与材料搭配使用能减少对方的毒副反应,文章将这种减毒关系归纳为“相畏相杀”。(5)文章得出了一个由七情配伍关系启发、基于作用关系分类的关于中药复合支架的全新视角,将中药传统观念引入组织工程领域,为后续复合支架的研究者提供新的研究思路,并在选材搭配方面提供一定的便利。展开更多
文摘Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.
基金supported by CNPq(303416/2018-1)and FAPESP(2019/25867-3).
文摘This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.Modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.
基金supported by Shahrekord University of Medical Sciences,Shahrekord,Iran(Ethics Code:IR.SKUMS.REC.1397.119,Grant No.3696 and Ethics Code:IR.SKUMS.REC.1401.197,Grant No.6651).
文摘Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.
文摘背景:如何修复骨缺损一直以来是临床难题,中药有效成分在骨修复方面具有良好的生物活性与治疗效果,将中药有效成分与组织工程材料相结合在骨修复领域具有广阔的前景。不同中药有效成分与支架的组合在作用关系方面具有相似之处。目的:搜集常见的中药有效成分与支架材料组合的案例,基于七情配伍的启发将组织工程支架与中药有效成分类比为产生配伍关系的两类中药,以二者的作用关系为纲进行归纳总结。方法:检索1998年1月至2024年1月Pub Med和中国知网数据库中发表的相关文献,英文检索词:“traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold”,中文检索词:“中药,中药有效成分,中药单体,骨组织工程,骨组织工程支架,支架,组织工程,骨缺损,骨修复”,最终纳入88篇文献进行综述分析。结果与结论:(1)组织工程支架材料与中药有效成分各自均在骨修复领域有广泛的运用,二者在成骨方面优势明显但仍有许多缺陷,许多研究致力于将二者制备成复合材料,希望通过二者间的相互作用发挥减毒增效作用。(2)一些药物与材料在成骨、抗菌、促血管生成方面能互相促进,增强原有的效果,受到传统方剂配伍观念的启发,文章将其归纳为“相须”关系,并举实例佐证。(3)一些药物能提高材料的强度,而某些材料能对负载于其上的药物实现缓释控释效果、增加载药量与稳定性,或是进行靶向递送,文章将这种单方面的提升效果归纳为“相使”关系。(4)一些中药与材料搭配使用能减少对方的毒副反应,文章将这种减毒关系归纳为“相畏相杀”。(5)文章得出了一个由七情配伍关系启发、基于作用关系分类的关于中药复合支架的全新视角,将中药传统观念引入组织工程领域,为后续复合支架的研究者提供新的研究思路,并在选材搭配方面提供一定的便利。
