In addition to their use in relieving the symptoms of various diseases,ketogenic diets(KDs)have also been adopted by healthy individuals to prevent being overweight.Herein,we reported that prolonged KD exposure induce...In addition to their use in relieving the symptoms of various diseases,ketogenic diets(KDs)have also been adopted by healthy individuals to prevent being overweight.Herein,we reported that prolonged KD exposure induced cardiac fibrosis.In rats,KD or frequent deep fasting decreased mitochondrial biogenesis,reduced cell respiration,and increased cardiomyocyte apoptosis and cardiac fibrosis.Mechanistically,increased levels of the ketone body β-hydroxybutyrate(β-OHB),an HDAC2 inhibitor,promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription.This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis,leading to cardiomyocyte apoptosis and cardiac fibrosis.展开更多
The underlying anticancer effects of butyrate,an end-product of the intestinal microbial fermentation of dietary fiber,remain elusive.Here,we report that butyrate promotes cancer cell apoptosis by acting as a SIRT3 in...The underlying anticancer effects of butyrate,an end-product of the intestinal microbial fermentation of dietary fiber,remain elusive.Here,we report that butyrate promotes cancer cell apoptosis by acting as a SIRT3 inhibitor.Butyrate inhibits SIRT3 both in cultured cells and in vitro.Butyrate-induced PDHA1 hyperacetylation relieves the inhibitory phosphorylation of PDHA1 at serine 293,thereby activating an influx of glycolytic intermediates into the tricarboxylic acid(TCA)cycle and reversing the Warburg effect.Meanwhile,butyrate-induced hyperacetylation inactivates complex I of the electron transfer chain and prevents the utilization of TCA cycle intermediates.These metabolic stresses promote apoptosis in hyperglycolytic cancer cells,such as HCT116p53^(−/−)cells.SIRT3 deacetylates both PDHA1 and complex I.Genetic ablation of Sirt3 in mouse hepatocytes abrogated the ability of butyrate to induce apoptosis.Our results identify a butyrate-mediated anti-tumor mechanism and indicate that the combined activation of PDC and inhibition of complex I is a novel tumor treatment strategy.展开更多
Dear Editor,Tetralogy of Fallot(TOF)is the most common complex congenital heart disease.Besides gene mutations and copy number variants,altered protein function induced by posttranscriptional or translational regulati...Dear Editor,Tetralogy of Fallot(TOF)is the most common complex congenital heart disease.Besides gene mutations and copy number variants,altered protein function induced by posttranscriptional or translational regulation also contributes to the onset of TOF.1 MiRNAs are short noncoding RNAs that bind to the 3’-UTR of target mRNAs to repress protein production.However,the causal link between miRNAs and TOF and the underlying mechanism has not been established.展开更多
Periconones B-E（1-4）,four new polyketide-terpenoid hybrid molecules were isolated from the endophytic fungus Periconia sp.F-31.Their structures and absolute configurations were established by extensive spectroscopic...Periconones B-E（1-4）,four new polyketide-terpenoid hybrid molecules were isolated from the endophytic fungus Periconia sp.F-31.Their structures and absolute configurations were established by extensive spectroscopic data analysis and electronic circular dichroism（ECD）.Compound 4 exhibited in vitro cytotoxic activity against the human MCF-7 tumor cell line with an IC_（50） value of 4.2 μmol/L,and compound 1 displayed anti-HIV activity with an IC_（50） value of 18.0 μmol/L.展开更多
基金supported by the Grants from the State Key Development Programs of Basic Research of China(Nos.2019YFA0801900,2018YFC100242,2018YFA080030,2018YFA0801300,and 2018YFC1004700)the National Natural Science Foundation of China(Nos.31871432,81771627,31521003,31821002,91753207,81722021,81471454,31671483,31671453,and 31425008)。
文摘In addition to their use in relieving the symptoms of various diseases,ketogenic diets(KDs)have also been adopted by healthy individuals to prevent being overweight.Herein,we reported that prolonged KD exposure induced cardiac fibrosis.In rats,KD or frequent deep fasting decreased mitochondrial biogenesis,reduced cell respiration,and increased cardiomyocyte apoptosis and cardiac fibrosis.Mechanistically,increased levels of the ketone body β-hydroxybutyrate(β-OHB),an HDAC2 inhibitor,promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription.This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis,leading to cardiomyocyte apoptosis and cardiac fibrosis.
基金This work was supported by the State Key Development Programs(973)of Basic Research of China(Nos.2012CB910103,2013CB531200,2013CB945401,2013CB911204,2015AA020913 and 2015CB943302)grants from the National Science Foundation of China(Nos.31330023,81301717,81471454,31425008,31521003 and 31671453)+1 种基金International Cooperative grant from Minister of Science and Technology(2014DFA30630)Science and Technology Municipal Commission of Shanghai(Nos.16JC1405300 and 15XD1400500).
文摘The underlying anticancer effects of butyrate,an end-product of the intestinal microbial fermentation of dietary fiber,remain elusive.Here,we report that butyrate promotes cancer cell apoptosis by acting as a SIRT3 inhibitor.Butyrate inhibits SIRT3 both in cultured cells and in vitro.Butyrate-induced PDHA1 hyperacetylation relieves the inhibitory phosphorylation of PDHA1 at serine 293,thereby activating an influx of glycolytic intermediates into the tricarboxylic acid(TCA)cycle and reversing the Warburg effect.Meanwhile,butyrate-induced hyperacetylation inactivates complex I of the electron transfer chain and prevents the utilization of TCA cycle intermediates.These metabolic stresses promote apoptosis in hyperglycolytic cancer cells,such as HCT116p53^(−/−)cells.SIRT3 deacetylates both PDHA1 and complex I.Genetic ablation of Sirt3 in mouse hepatocytes abrogated the ability of butyrate to induce apoptosis.Our results identify a butyrate-mediated anti-tumor mechanism and indicate that the combined activation of PDC and inhibition of complex I is a novel tumor treatment strategy.
基金supported by grants from the National Key R&D Program of China(2021YFC2701101,H.W.)the National Natural Science Foundation of China(81930036 and 82150008,H.W.)the Commission for Science and Technology of Shanghai Municipality(20JC1418500,H.W.).
文摘Dear Editor,Tetralogy of Fallot(TOF)is the most common complex congenital heart disease.Besides gene mutations and copy number variants,altered protein function induced by posttranscriptional or translational regulation also contributes to the onset of TOF.1 MiRNAs are short noncoding RNAs that bind to the 3’-UTR of target mRNAs to repress protein production.However,the causal link between miRNAs and TOF and the underlying mechanism has not been established.
文摘Periconones B-E（1-4）,four new polyketide-terpenoid hybrid molecules were isolated from the endophytic fungus Periconia sp.F-31.Their structures and absolute configurations were established by extensive spectroscopic data analysis and electronic circular dichroism（ECD）.Compound 4 exhibited in vitro cytotoxic activity against the human MCF-7 tumor cell line with an IC_（50） value of 4.2 μmol/L,and compound 1 displayed anti-HIV activity with an IC_（50） value of 18.0 μmol/L.
