The aim of this study was to develop an intravenous clarithromycin lipid emulsion(CLE)with good stability and excellent antibacterial activity. The CLE was prepared by the thinfilm dispersed homogenization method. The...The aim of this study was to develop an intravenous clarithromycin lipid emulsion(CLE)with good stability and excellent antibacterial activity. The CLE was prepared by the thinfilm dispersed homogenization method. The interaction between clarithromycin(CLA) and cholesteryl hemisuccinate(CHEMS) was confirmed by DSC, FT-IR and^1H NMR analysis. The interfacial drug loading, thermal sterilization, freeze–thaw stability, and in vitro and in vivo antibacterial activity were investigated systematically. DSC, FT-IR and^1H NMR spectra showed that CHEMS(CLA: CHEMS, M ratio 1:2) could interact with CLA through H-bonding and a hydrogen-bonded ion pair. The CHEMS was found necessary to maintain the stability of CLE.Ultracentrifugation showed that almost 88% CLA could be loaded into the interfacial layer.The optimized CLE formulation could withstand autoclaving at 121 °C for 10 min and remain stable after three freeze–thaw cycles. The in vitro susceptibility test revealed that the CLA–CHEMS ion-pair and CLE have similar activity to the parent drug against many different bacterial strains. The in vivo antibacterial activity showed that the ED50 of intravenous CLE was markedly lower than that of CLA solution administrated orally. CLE exhibited pronounced antibacterial activity and might be a candidate for a new nanocarrier for CLA with potential advantages over the current commercial formulation.展开更多
Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to inv...Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.展开更多
Type 2 diabetes mellitus(T2DM)and nonalcoholic fatty liver disease(NAFLD)are the most problematic metabolic diseases in the world.NAFLD encompasses a spectrum of severity,ranging from simple steatosis to non-alcoholic...Type 2 diabetes mellitus(T2DM)and nonalcoholic fatty liver disease(NAFLD)are the most problematic metabolic diseases in the world.NAFLD encompasses a spectrum of severity,ranging from simple steatosis to non-alcoholic steatohepatitis(NASH)and fibrosis,increasing the risk of cirrhosis and hepatocellular carcinoma.Importantly,NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM.T2DM and NAFLD(T2DM-NAFLD)are called as the Xike Rixijing Disease and Tonglaga Indigestion Disease respectively,in Mongolian medicine.Xike Rixijing Disease maybe develop into Tonglaga Indigestion Disease.Forturnately many Mongolian medicines show efficient treatment of T2DM-NAFLD,such as Agriophyllum squarrosum,Haliyasu(dried powder of camel placenta),Digeda-4(herbs of Lomatogonium carinthiacum,rhizomata of Coptis chinensis,ripe fruits of Gardenia jasminoides,herbs of Dianthus superbus),Guangmingyan Siwei Decoction Powder(Halite,ripe fruits of Terminalia chebula,rhizomata of Zingiber officinale,fruit clusters of Piper longum),Tonglaga-5(ripe fruits of Punica granatum,barks of Cinnamomum cassia,ripe fruits of Amomum kravanh,fruit clusters of Piper longum,fowers of Carthamus tinctorius),Tegexidegeqi(rhizomata of Inula helenium,ripe fruits of Gardenia jasminoides,rhizomata of Platycodon grandiflorum,rhizomata of Coptis chinensis,heartwood of Caesalpinia sappan),Ligan Shiliu Bawei San(ripe fruits of Punica granatum,barks of Cinnamomum cassia,ripe fruits of Amomum kravanh,fruit clusters of Piper longum,fowers of Carthamus tinctorius,ripe fruits of Amomum tsao-ko,rhizomata of Zingiber officinale),etc.Principles of Mongolian medicine in treating diseases:by balancing“three essences or roots”and“seven elements”,strengthening liver and kidney function,transporting nutrients to enhance physical strength and disease resistance,and combined with drugs for comprehensive conditioning treatment.However,their molecular mechanisms remain unclear.In this review,we prospect that Mongolian medicines might be a promising treatment for T2DM-NAFLD by activating P2X7R/NLRP3/NF-κB infammatory pathway via lipid-sensitive nuclear receptors(i.e.,FXR and LXR).展开更多
5-Methylcytosine(m^(5)C)is one of the most prevalent internal modifications of messenger RNA(mRNA)in higher eukaryotes.Here we report that Y box protein 2(YBX2)serves as a novel mammalian m^(5)C binding protein to und...5-Methylcytosine(m^(5)C)is one of the most prevalent internal modifications of messenger RNA(mRNA)in higher eukaryotes.Here we report that Y box protein 2(YBX2)serves as a novel mammalian m^(5)C binding protein to undergo liquid-liquid phase separation(LLPS)both in vivo and in vitro,and this YBX2-dependent LLPS is enhanced by m^(5)C marked RNA.Furthermore,the crystal structure assay revealed that W100,as a distinct m^(5)C binding site of YBX2,is critical in mediating YBX2 phase separation.Our study resolved the relationship between RNA m^(5)C and phase separation,providing a clue for a new regulatory layer of epigenetics.展开更多
文摘The aim of this study was to develop an intravenous clarithromycin lipid emulsion(CLE)with good stability and excellent antibacterial activity. The CLE was prepared by the thinfilm dispersed homogenization method. The interaction between clarithromycin(CLA) and cholesteryl hemisuccinate(CHEMS) was confirmed by DSC, FT-IR and^1H NMR analysis. The interfacial drug loading, thermal sterilization, freeze–thaw stability, and in vitro and in vivo antibacterial activity were investigated systematically. DSC, FT-IR and^1H NMR spectra showed that CHEMS(CLA: CHEMS, M ratio 1:2) could interact with CLA through H-bonding and a hydrogen-bonded ion pair. The CHEMS was found necessary to maintain the stability of CLE.Ultracentrifugation showed that almost 88% CLA could be loaded into the interfacial layer.The optimized CLE formulation could withstand autoclaving at 121 °C for 10 min and remain stable after three freeze–thaw cycles. The in vitro susceptibility test revealed that the CLA–CHEMS ion-pair and CLE have similar activity to the parent drug against many different bacterial strains. The in vivo antibacterial activity showed that the ED50 of intravenous CLE was markedly lower than that of CLA solution administrated orally. CLE exhibited pronounced antibacterial activity and might be a candidate for a new nanocarrier for CLA with potential advantages over the current commercial formulation.
基金supported by the National Natural Science Foundation of China(No.81402858)the Liaoning Natural Science Foundation(No.2015020736)Shenyang Pharmaceutical University Long-term Training Fund(No.ZCJJ2014406)
文摘Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.
基金This work was supported by grants from the National Natural Science Foundation of China （91019021 and 81430069 to J.C.）, the National Basic Research Program of China （973 Program） （2013CB910902 to J.C.）, Shanghai Committee of Science and Technology （15ZR1424500 to T.W. and 15140904300）, Shanghai Municipal Education Commission （ZZjdyx15003 to T.W. and 2017-01-07-00-01-E00050 to J.C.）, and Shanghai Jiao Tong University School of Medicine （14XJ10001 to T.W.）.
基金supported by the National Natural Science Foundation of China (Grant numbers 82004070,82160814)the Science and Technology Project of Inner Mongolia (Grant numbers 2020GG0103)+3 种基金the Natural Science Foundation of Inner Mongolia(Grant numbers 2018MS08123)the Mongolian Medicine R&D National and Local Joint Engineering Research Center Open Fund Project (Grant numbers MDK2020001,MDK2021023)Science and Technology Research Project of Higher Education of Inner Mongolia Autonomous Region (Grant numbers NJZY21641)Science and Technology Project of Tongliao (Grant numbers TLKJ2020001)
文摘Type 2 diabetes mellitus(T2DM)and nonalcoholic fatty liver disease(NAFLD)are the most problematic metabolic diseases in the world.NAFLD encompasses a spectrum of severity,ranging from simple steatosis to non-alcoholic steatohepatitis(NASH)and fibrosis,increasing the risk of cirrhosis and hepatocellular carcinoma.Importantly,NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM.T2DM and NAFLD(T2DM-NAFLD)are called as the Xike Rixijing Disease and Tonglaga Indigestion Disease respectively,in Mongolian medicine.Xike Rixijing Disease maybe develop into Tonglaga Indigestion Disease.Forturnately many Mongolian medicines show efficient treatment of T2DM-NAFLD,such as Agriophyllum squarrosum,Haliyasu(dried powder of camel placenta),Digeda-4(herbs of Lomatogonium carinthiacum,rhizomata of Coptis chinensis,ripe fruits of Gardenia jasminoides,herbs of Dianthus superbus),Guangmingyan Siwei Decoction Powder(Halite,ripe fruits of Terminalia chebula,rhizomata of Zingiber officinale,fruit clusters of Piper longum),Tonglaga-5(ripe fruits of Punica granatum,barks of Cinnamomum cassia,ripe fruits of Amomum kravanh,fruit clusters of Piper longum,fowers of Carthamus tinctorius),Tegexidegeqi(rhizomata of Inula helenium,ripe fruits of Gardenia jasminoides,rhizomata of Platycodon grandiflorum,rhizomata of Coptis chinensis,heartwood of Caesalpinia sappan),Ligan Shiliu Bawei San(ripe fruits of Punica granatum,barks of Cinnamomum cassia,ripe fruits of Amomum kravanh,fruit clusters of Piper longum,fowers of Carthamus tinctorius,ripe fruits of Amomum tsao-ko,rhizomata of Zingiber officinale),etc.Principles of Mongolian medicine in treating diseases:by balancing“three essences or roots”and“seven elements”,strengthening liver and kidney function,transporting nutrients to enhance physical strength and disease resistance,and combined with drugs for comprehensive conditioning treatment.However,their molecular mechanisms remain unclear.In this review,we prospect that Mongolian medicines might be a promising treatment for T2DM-NAFLD by activating P2X7R/NLRP3/NF-κB infammatory pathway via lipid-sensitive nuclear receptors(i.e.,FXR and LXR).
基金the National Natural Science Foundation of China(Grants No.32030058,91940302,91940304,91940000 and 92053115)the fellowship of China Postdoctoral Science Foundation(Grant No.2020M670986)+3 种基金the National Key R&D Program of China(Grants No.2018YFA0109700,2019YFA0801702 and 2019YFA0802201)Beijing Nova Program(Grant No.Z201100006820104)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.CAS2018133)the Open Research Fund of the National Center for Protein Sciences at Peking University in Beijing.We thank the National Center for Protein Science Shanghai for their instrumental support and technical assistance.We thank the staff from the BL18U1 beamline at Shanghai Synchrotron Radiation Facility for assistance during data collection.
文摘5-Methylcytosine(m^(5)C)is one of the most prevalent internal modifications of messenger RNA(mRNA)in higher eukaryotes.Here we report that Y box protein 2(YBX2)serves as a novel mammalian m^(5)C binding protein to undergo liquid-liquid phase separation(LLPS)both in vivo and in vitro,and this YBX2-dependent LLPS is enhanced by m^(5)C marked RNA.Furthermore,the crystal structure assay revealed that W100,as a distinct m^(5)C binding site of YBX2,is critical in mediating YBX2 phase separation.Our study resolved the relationship between RNA m^(5)C and phase separation,providing a clue for a new regulatory layer of epigenetics.
