BACKGROUND Indole-3-carbinol(I3C)and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models,including colitis indu...BACKGROUND Indole-3-carbinol(I3C)and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models,including colitis induced by dextran sulfate sodium(DSS).MicroRNAs(miRNAs)are also gaining traction as potential therapeutic agents or diagnostic elements.Enterohepatic Helicobacter(EHH)species are associated with an increased risk of inflammatory bowel disease,but little is known about how these species affect the immune system or response to treatment.AIM To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH species compare with responses to DSS and inflammatory bowel disease.METHODS We infected C57BL/6 mice with Helicobacter muridarum(H.muridarum),with and without DSS and I3C treatment.Pathological responses were evaluated by histological examination,symptom scores,and cytokine responses.MiRNAs analysis was performed on mesenteric lymph nodes to further evaluate the regional immune response.RESULTS H.muridarum infection alone caused colonic inflammation and upregulated proinflammatory,macrophage-associated cytokines in the colon similar to changes seen in DSS-treated mice.Further upregulation occurred upon treatment with DSS.H.muridarum infection caused broad changes in mesenteric lymph node miRNA expression,but colitis-associated miRNAs were regulated similarly in H.muridarum-infected and uninfected,DSS-treated mice.In spite of causing colitis exacerbation,H.muridarum infection did not prevent disease amelioration by I3C.I3C normalized both macrophage-and T cell-associated cytokines.CONCLUSION Thus,I3C may be useful for inflammatory bowel disease patients regardless of EHH infection.The miRNA changes associated with I3C treatment are likely the result of,rather than the cause of immune response changes.展开更多
Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to...Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation,including local facial amphiphilicity and global amphiphilicity.This work conceptualizes Facial Amphiphilicity Index(FAI)as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy.FAI is a ratio of numbers of charges to rings,representing both compositions of hydrophilicity and hydrophobicity.Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria.Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs.Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid.While low and high FAIs respectively lead to higher and lower antimicrobial efficacy,in consideration of cytotoxicity,the sweet spot is typically suited with intermediate FAIs for each specific system.This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes.The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.展开更多
Recent evidence indicates that different types of vascular stem cells （VSCs） reside within the mural layers of arteries and veins. The precise identities of these resident VSCs are still unclear; generally, postnata...Recent evidence indicates that different types of vascular stem cells （VSCs） reside within the mural layers of arteries and veins. The precise identities of these resident VSCs are still unclear; generally, postnatal vasculature contains multilineage stem cells and vascular cell lineage-specific progenitor/stem cells which may participate in both vascular repair and lesion formation. However, the underlying mechanism remains poorly understood. In this review, we summarize the potential molecular mechanisms, which may control the quiescence and activation of resident VSCs and highlight a notion that the differential states of resident VSCs are directly linked to vascular repair or lesion formation.展开更多
基金Supported by the National Institutes of Health,No.P20GM103641.
文摘BACKGROUND Indole-3-carbinol(I3C)and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models,including colitis induced by dextran sulfate sodium(DSS).MicroRNAs(miRNAs)are also gaining traction as potential therapeutic agents or diagnostic elements.Enterohepatic Helicobacter(EHH)species are associated with an increased risk of inflammatory bowel disease,but little is known about how these species affect the immune system or response to treatment.AIM To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH species compare with responses to DSS and inflammatory bowel disease.METHODS We infected C57BL/6 mice with Helicobacter muridarum(H.muridarum),with and without DSS and I3C treatment.Pathological responses were evaluated by histological examination,symptom scores,and cytokine responses.MiRNAs analysis was performed on mesenteric lymph nodes to further evaluate the regional immune response.RESULTS H.muridarum infection alone caused colonic inflammation and upregulated proinflammatory,macrophage-associated cytokines in the colon similar to changes seen in DSS-treated mice.Further upregulation occurred upon treatment with DSS.H.muridarum infection caused broad changes in mesenteric lymph node miRNA expression,but colitis-associated miRNAs were regulated similarly in H.muridarum-infected and uninfected,DSS-treated mice.In spite of causing colitis exacerbation,H.muridarum infection did not prevent disease amelioration by I3C.I3C normalized both macrophage-and T cell-associated cytokines.CONCLUSION Thus,I3C may be useful for inflammatory bowel disease patients regardless of EHH infection.The miRNA changes associated with I3C treatment are likely the result of,rather than the cause of immune response changes.
文摘Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation,including local facial amphiphilicity and global amphiphilicity.This work conceptualizes Facial Amphiphilicity Index(FAI)as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy.FAI is a ratio of numbers of charges to rings,representing both compositions of hydrophilicity and hydrophobicity.Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria.Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs.Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid.While low and high FAIs respectively lead to higher and lower antimicrobial efficacy,in consideration of cytotoxicity,the sweet spot is typically suited with intermediate FAIs for each specific system.This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes.The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.
文摘Recent evidence indicates that different types of vascular stem cells （VSCs） reside within the mural layers of arteries and veins. The precise identities of these resident VSCs are still unclear; generally, postnatal vasculature contains multilineage stem cells and vascular cell lineage-specific progenitor/stem cells which may participate in both vascular repair and lesion formation. However, the underlying mechanism remains poorly understood. In this review, we summarize the potential molecular mechanisms, which may control the quiescence and activation of resident VSCs and highlight a notion that the differential states of resident VSCs are directly linked to vascular repair or lesion formation.
