AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD) alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited ...AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD) alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16 S r DNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR,and intergroup comparison was conducted by R software.RESULTS After being on KD treatment for a week,64% of epileptic infants showed an obvious improvement,with a 50% decrease in seizure frequency. GM structure in epileptic infants(P1 group) differed dramatically from that in healthy infants(Health group). Proteobacteria,which had accumulated significantly in the P1 group,decreased dramatically after KD treatment(P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group,in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.展开更多
AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2(B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model.METHODS Ovalbumin(OVA)-indu...AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2(B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model.METHODS Ovalbumin(OVA)-induced allergic asthma and b-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin(HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVAspecific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid(BALF) were also assessed. In the food allergy mouse model, the levels of total Ig E and cytokines in serum were measured.RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total Ig E in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4(IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed.CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.展开更多
Thoracic aortic aneurysms(TAAs)develop asymptomatically and are characterized by dilatation of the aorta.This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective tre...Thoracic aortic aneurysms(TAAs)develop asymptomatically and are characterized by dilatation of the aorta.This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments.The current understanding of the pathogenesis of TAA is still limited,especially for sporadic TAAs without known genetic mutation.Sirtuin 6(SIRT6)expression was significantly decreased in the tunica media of sporadic human TAA tissues.Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture,reduced survival,and increased vascular inflammation and senescence after angiotensin II infusion.Transcriptome analysis identified interleukin(IL)-1βas a pivotal target of SIRT6,and increased IL-1βlevels correlated with vascular inflammation and senescence in human and mouse TAA samples.Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation.Genetic knockout of Il1b or pharmacological inhibition of IL-1βsignaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation,senescence,TAA formation and survival in mice.The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence,providing insight into potential epigenetic strategies for TAA treatment.展开更多
基金Supported by the Innovation Fund of Science and Technology Commission of Shenzhen Municipality,China,No.JCYJ-2015-0403100317071
文摘AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD) alters GM.METHODS A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16 S r DNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR,and intergroup comparison was conducted by R software.RESULTS After being on KD treatment for a week,64% of epileptic infants showed an obvious improvement,with a 50% decrease in seizure frequency. GM structure in epileptic infants(P1 group) differed dramatically from that in healthy infants(Health group). Proteobacteria,which had accumulated significantly in the P1 group,decreased dramatically after KD treatment(P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group,in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.
基金Supported by Basic Science Research Program funded by The Innovation of Science and Technology Commission of Shenzhen Municipality,China,No.JCYJ20120828092009036Shenzhen Science and Technology Project,No.JCYJ20150403100317067
文摘AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2(B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model.METHODS Ovalbumin(OVA)-induced allergic asthma and b-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin(HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVAspecific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid(BALF) were also assessed. In the food allergy mouse model, the levels of total Ig E and cytokines in serum were measured.RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total Ig E in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4(IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed.CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.
基金This work was supported by grants from the National Key Research and Development Project of China(grant numbers:2020YFC2008003,2021YFA0804900 and 2019YFA0801500)the National Natural Science Foundation of China(grant numbers:92149305,8222500782030017 and 81801627)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(grant numbers:2021-I2M-1-016,2022-RC180-03,2022-I2M-JB-006 and 2022-I2M-2-002).
文摘Thoracic aortic aneurysms(TAAs)develop asymptomatically and are characterized by dilatation of the aorta.This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments.The current understanding of the pathogenesis of TAA is still limited,especially for sporadic TAAs without known genetic mutation.Sirtuin 6(SIRT6)expression was significantly decreased in the tunica media of sporadic human TAA tissues.Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture,reduced survival,and increased vascular inflammation and senescence after angiotensin II infusion.Transcriptome analysis identified interleukin(IL)-1βas a pivotal target of SIRT6,and increased IL-1βlevels correlated with vascular inflammation and senescence in human and mouse TAA samples.Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation.Genetic knockout of Il1b or pharmacological inhibition of IL-1βsignaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation,senescence,TAA formation and survival in mice.The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence,providing insight into potential epigenetic strategies for TAA treatment.
