Biochanin A(BCA) and CPe-Ⅲ peptide, which both exist in chickpea(Cicer arietinum L.), possess significant antihyperlipidemic properties. However, the actualmechanisms ofthose compounds in inhibiting the dysregulation...Biochanin A(BCA) and CPe-Ⅲ peptide, which both exist in chickpea(Cicer arietinum L.), possess significant antihyperlipidemic properties. However, the actualmechanisms ofthose compounds in inhibiting the dysregulation oflipid metabolism and complicated inflammation have not been wellcharacterized. This study investigated the effects ofBCA, CPe-Ⅲ peptide, and combined BCA and CPe-Ⅲ peptide(BC) on the expression ofgenes involved in hepatic lipid and inflammation metabolism. Results demonstrated that BCA, CPe-Ⅲ peptide, and BC significantly attenuated hepatitis and hyperlipidemia by downregulating those genes involved in pro-inflammatory cytokines(TNF-α), hepatic fatty acid(FA) synthesis(ACC1 and FAS), cholesterolmetabolism(SREBP2, HMGCR, and PCSK9), and upregulating key regulators involved in FA oxidation(PPARα and FABP1), lipolysis(ATGL), LDLR, reverse cholesteroltransport(ABCA1, SR-B1, and LXRα), and cholesterolcatabolism(CYP7 A1). Moreover, they also altered the expression oflipid metabolism-related proteins, including SREBP2, PCSK9, LDLR, ABCA1, and CYP7 A1. Finally, these results revealed that the combination treatment ofBCA and CPe-Ⅲ peptide resulted in greater antihyperlipidemic activity compared with individualcompounds.展开更多
Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptid...Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.展开更多
Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chr...Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.展开更多
基金supported by National Natural Science Foundation of China (Nos. 31571825, 31271979, and 31201245)Natural Science Foundation of Tianjin, China (No. 15JCYBJC30100)
文摘Biochanin A(BCA) and CPe-Ⅲ peptide, which both exist in chickpea(Cicer arietinum L.), possess significant antihyperlipidemic properties. However, the actualmechanisms ofthose compounds in inhibiting the dysregulation oflipid metabolism and complicated inflammation have not been wellcharacterized. This study investigated the effects ofBCA, CPe-Ⅲ peptide, and combined BCA and CPe-Ⅲ peptide(BC) on the expression ofgenes involved in hepatic lipid and inflammation metabolism. Results demonstrated that BCA, CPe-Ⅲ peptide, and BC significantly attenuated hepatitis and hyperlipidemia by downregulating those genes involved in pro-inflammatory cytokines(TNF-α), hepatic fatty acid(FA) synthesis(ACC1 and FAS), cholesterolmetabolism(SREBP2, HMGCR, and PCSK9), and upregulating key regulators involved in FA oxidation(PPARα and FABP1), lipolysis(ATGL), LDLR, reverse cholesteroltransport(ABCA1, SR-B1, and LXRα), and cholesterolcatabolism(CYP7 A1). Moreover, they also altered the expression oflipid metabolism-related proteins, including SREBP2, PCSK9, LDLR, ABCA1, and CYP7 A1. Finally, these results revealed that the combination treatment ofBCA and CPe-Ⅲ peptide resulted in greater antihyperlipidemic activity compared with individualcompounds.
基金the National Key R&D Program of China(No.2022YFA1302900 to H.Liu)National Natural Science Foundation of China(Nos.82130105,22337003,82121005 to H.Liu+2 种基金and Nos.22177124,82322063 to J.Wang)Program of Shang-hai Academic Research Leader(No.23XD1460300 to J.Wang)the Lingang Laboratory(No.LG-GG-202204-02 to J.Wang)for supporting this work.We would like to acknowledge Shanghai Highline Therapeutics.
文摘Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.
文摘Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.
