This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice.Newborn BALB/c mice were assigned to the control group(administration s...This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice.Newborn BALB/c mice were assigned to the control group(administration saline)and the CCFM1078 group(administration B.breve CCFM1078,3×10^(9) CFU/day)in 3-,4-,and 5-week tests.All the groups have male and female distinctions.Our findings demonstrate that B.breve CCFM1078 exerts on the dynamic equilibrium between bone formation and resorption during the critical period of growth in mice by modulating the composition of gut microbiota and metabolites(hexadecanamide,linoleoyl ethanolamide,and palmitoyl ethanolamide),the genes and proteins expression related to the growth hormone(GH)/insulin-like growth factors-1(IGF-1)axis and Gs/PKA/CREB signaling pathways,as well as downstream osteogenic and osteoclastic differentiation factors.The effects of B.breve CCFM1078 were different with age and gender dependent.This finding suggests B.breve CCFM1078 may have potential applications in regulating bone metabolism in the growth period population.展开更多
Chlorinated polyfluorinated ether sulfonate(F-53B),a chromium-fog depressant widely utilized as an alternative to perfluorooctanesulfonate,can transfer from mother to fetus.Recent research has demonstrated that prenat...Chlorinated polyfluorinated ether sulfonate(F-53B),a chromium-fog depressant widely utilized as an alternative to perfluorooctanesulfonate,can transfer from mother to fetus.Recent research has demonstrated that prenatal exposure to F-53B results in synaptic damage in weaning mice.However,the mechanism underpinning F-53B-triggered synaptic damage during fetal development remains unclear.This study aims to investigate the role of the protein kinase A(PKA)/cAMP response element-binding protein(CREB)pathway,a crucial signaling mechanism known as“synaptic switch”,in the early neurotoxicity of F-53B exposure both in vivo and in vitro.Here,C57BL/6 fetal mice were subjected to exposure to F-53B(0,4,and 40μg/L)from gestation days(GD)0 to 14 to evaluate nerve injury prior to delivery.HT22 neurons exposed to F-53B(0,0.016,0.08,0.4,2,and 10μmol/L)for 24 h were utilized to elucidate the underlying mechanism.Our results demonstrated that F-53B significantly increased the fluorescence intensity of Nestin(a neural stem cell marker)in the fetal brain hippocampus(GD14).Subsequently,we found that F-53B downregulated the expression of synaptic plasticity markers(SYP,GAP43,and BDNF)in the fetal brain and HT22 neurons.Further molecular docking analysis revealed that F-53B fits into the ligand-binding pockets of PKA and CREB1.Results showed that F-53B inhibited the translocation of PKA protein from the cytoplasm to the neuronal nuclei and reduced the levels of PKA,CREB1,p-PKA(α/β/γ)-Thr197,and p-CREB1-S133 in the nucleus.Furthermore,the expression of synaptic plasticity markers altered by F-53B could be reversed by a PKA agonist and was intensified by a PKA antagonist.In summary,our findings suggest that intrauterine exposure to F-53B can weaken the expression of synaptic plasticity markers in the fetal brain,with this neurotoxicity being mediated by the cytoplasmic retention of PKA.展开更多
基金supported by the National Key R&D Program of China(2021YFD2100700)National Natural Science Foundation of China(32021005)+1 种基金111 project(BP0719028)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice.Newborn BALB/c mice were assigned to the control group(administration saline)and the CCFM1078 group(administration B.breve CCFM1078,3×10^(9) CFU/day)in 3-,4-,and 5-week tests.All the groups have male and female distinctions.Our findings demonstrate that B.breve CCFM1078 exerts on the dynamic equilibrium between bone formation and resorption during the critical period of growth in mice by modulating the composition of gut microbiota and metabolites(hexadecanamide,linoleoyl ethanolamide,and palmitoyl ethanolamide),the genes and proteins expression related to the growth hormone(GH)/insulin-like growth factors-1(IGF-1)axis and Gs/PKA/CREB signaling pathways,as well as downstream osteogenic and osteoclastic differentiation factors.The effects of B.breve CCFM1078 were different with age and gender dependent.This finding suggests B.breve CCFM1078 may have potential applications in regulating bone metabolism in the growth period population.
基金supported by the National Science Foundation of China(No.82073503,82173471,82003409,82103823)the Natural Science Foundation of Guangdong Province(No.2021B1515020015,2021A1515012212)the Guangzhou Science and Technology Plan Project(No.2024A04J6476).
文摘Chlorinated polyfluorinated ether sulfonate(F-53B),a chromium-fog depressant widely utilized as an alternative to perfluorooctanesulfonate,can transfer from mother to fetus.Recent research has demonstrated that prenatal exposure to F-53B results in synaptic damage in weaning mice.However,the mechanism underpinning F-53B-triggered synaptic damage during fetal development remains unclear.This study aims to investigate the role of the protein kinase A(PKA)/cAMP response element-binding protein(CREB)pathway,a crucial signaling mechanism known as“synaptic switch”,in the early neurotoxicity of F-53B exposure both in vivo and in vitro.Here,C57BL/6 fetal mice were subjected to exposure to F-53B(0,4,and 40μg/L)from gestation days(GD)0 to 14 to evaluate nerve injury prior to delivery.HT22 neurons exposed to F-53B(0,0.016,0.08,0.4,2,and 10μmol/L)for 24 h were utilized to elucidate the underlying mechanism.Our results demonstrated that F-53B significantly increased the fluorescence intensity of Nestin(a neural stem cell marker)in the fetal brain hippocampus(GD14).Subsequently,we found that F-53B downregulated the expression of synaptic plasticity markers(SYP,GAP43,and BDNF)in the fetal brain and HT22 neurons.Further molecular docking analysis revealed that F-53B fits into the ligand-binding pockets of PKA and CREB1.Results showed that F-53B inhibited the translocation of PKA protein from the cytoplasm to the neuronal nuclei and reduced the levels of PKA,CREB1,p-PKA(α/β/γ)-Thr197,and p-CREB1-S133 in the nucleus.Furthermore,the expression of synaptic plasticity markers altered by F-53B could be reversed by a PKA agonist and was intensified by a PKA antagonist.In summary,our findings suggest that intrauterine exposure to F-53B can weaken the expression of synaptic plasticity markers in the fetal brain,with this neurotoxicity being mediated by the cytoplasmic retention of PKA.
