Rana kunyuensis is a species of brown frog that lives exclusively on Kunyu Mountain,Yantai,China.In the current study,a 279-bp cDNA sequence encoding a novel antimicrobial peptide (AMP),designated as amurin-9KY,was cl...Rana kunyuensis is a species of brown frog that lives exclusively on Kunyu Mountain,Yantai,China.In the current study,a 279-bp cDNA sequence encoding a novel antimicrobial peptide (AMP),designated as amurin-9KY,was cloned from synthesized double-strand skin cDNA of R.kunyuensis.The amurin-9KY precursor was composed of 62 amino acid (aa) residues,whereas the mature peptide was composed of 14 aa and contained two cysteines forming a C-terminal heptapeptide ring (Rana box domain) and an amidated C-terminus.These structural characters represent a novel amphibian AMP family.Although amurin-9KY exhibited high similarity to the already identified amurin-9AM from R.amurensis,little is known about the structures and activities of amurin-9 family AMPs so far.Therefore,amurin-9KY and its three derivatives (amurin-9KY1-3) were designed and synthesized.The structures and activities were examined to evaluate the influence of C-terminal amidation and the heptapeptide ring on the activities and structure of amurin-9KY..Results indicated that C-terminal amidation was essential for antimicrobial activity,whereas both C-terminal amidation and the heptapeptide ring played roles in the low hemolytic activity.Circular dichroism (CD) spectra showed that the four peptides adopted an α-helical conformation in THF/H2O (v/v 1∶1) solution,but a random coil in aqueous solution.Elimination of the C-terminal heptapeptide ring generated two free cysteine residues with unpaired thiol groups,which greatly increased the concentration-dependent anti-oxidant activity.Scanning electron microscopy (SEM) was also performed to determine the possible bactericidal mechanisms.展开更多
Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effe...Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.展开更多
A C/D ring synthon of vitamin D is readily obtained from cholesteryl acetate via oxidation, elimination of acetoxy group and Norrish type II photochemical reaction.
In this paper,we use rB,lM,SM,Iu to determine some relationships between the structure of the module M and the stracture of the ring B for a double RMs,where M is a faithful module,If B=End (RM),then we get some prope...In this paper,we use rB,lM,SM,Iu to determine some relationships between the structure of the module M and the stracture of the ring B for a double RMs,where M is a faithful module,If B=End (RM),then we get some proper ties of the endomorphism ring of the modules.展开更多
基金supported by grants from the National Natural Science Foundation of China(31772455)Natural Science Foundation of Jiangsu Province(BK20160336and BK20171214)+1 种基金Natural Science Foundation of College in Jiangsu Province(16KJB350004)Suzhou Science and Technology Development Project(SYN201504 and SNG2017045)
文摘Rana kunyuensis is a species of brown frog that lives exclusively on Kunyu Mountain,Yantai,China.In the current study,a 279-bp cDNA sequence encoding a novel antimicrobial peptide (AMP),designated as amurin-9KY,was cloned from synthesized double-strand skin cDNA of R.kunyuensis.The amurin-9KY precursor was composed of 62 amino acid (aa) residues,whereas the mature peptide was composed of 14 aa and contained two cysteines forming a C-terminal heptapeptide ring (Rana box domain) and an amidated C-terminus.These structural characters represent a novel amphibian AMP family.Although amurin-9KY exhibited high similarity to the already identified amurin-9AM from R.amurensis,little is known about the structures and activities of amurin-9 family AMPs so far.Therefore,amurin-9KY and its three derivatives (amurin-9KY1-3) were designed and synthesized.The structures and activities were examined to evaluate the influence of C-terminal amidation and the heptapeptide ring on the activities and structure of amurin-9KY..Results indicated that C-terminal amidation was essential for antimicrobial activity,whereas both C-terminal amidation and the heptapeptide ring played roles in the low hemolytic activity.Circular dichroism (CD) spectra showed that the four peptides adopted an α-helical conformation in THF/H2O (v/v 1∶1) solution,but a random coil in aqueous solution.Elimination of the C-terminal heptapeptide ring generated two free cysteine residues with unpaired thiol groups,which greatly increased the concentration-dependent anti-oxidant activity.Scanning electron microscopy (SEM) was also performed to determine the possible bactericidal mechanisms.
基金Supported by Brazilian government research foundations National Council for Research and Technology and Coordination for the Improvement of Higher Education Personnel with research grant and scholarships processNo.9028-11-0+2 种基金No.305064/2011-8 and No.232711/2014-3Sao Paulo Government agency Sao Paulo State Research Foundation withprocess No.2011/12448-0both granted to Andrade LEC and Keppeke GD
文摘Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.
文摘A C/D ring synthon of vitamin D is readily obtained from cholesteryl acetate via oxidation, elimination of acetoxy group and Norrish type II photochemical reaction.
文摘In this paper,we use rB,lM,SM,Iu to determine some relationships between the structure of the module M and the stracture of the ring B for a double RMs,where M is a faithful module,If B=End (RM),then we get some proper ties of the endomorphism ring of the modules.
