A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidat...A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.展开更多
A new degraded sesquiterpene was isolated from the marine actinomycete Streptomyces sp. 0616208. Its structure was elucidated as （1α; 4aα; 5α, 7β, 8aβ）-5, 8a-dimethyl-decahydrona- phthalene-1, 4a, 7-triol on th...A new degraded sesquiterpene was isolated from the marine actinomycete Streptomyces sp. 0616208. Its structure was elucidated as （1α; 4aα; 5α, 7β, 8aβ）-5, 8a-dimethyl-decahydrona- phthalene-1, 4a, 7-triol on the basis of spectroscopic data.展开更多
In the present investigation, a total number of 132 different actinomycetes strains were isolated from the humus soil samples. Out of 132 isolates, 52 showed inhibitory activity against the fungal pathogen Rhizoctonia...In the present investigation, a total number of 132 different actinomycetes strains were isolated from the humus soil samples. Out of 132 isolates, 52 showed inhibitory activity against the fungal pathogen Rhizoctonia solani. Among the antagonists, the isolate designated as AM-S1 exhibited maximum inhibitory activity against the test pathogen R. solani (41 mm). Further, the light microscopic observations of the co-cultures showed severe structural alterations in the mycelia of R. solani near the zone of inhibition. The isolate AM-S1 was identified as Streptomyces sp. by morphological and 16S rDNA sequence analysis. The color of the aerial and substrate mycelia produced by the Streptomyces sp. AM-S1 varied with different media. The isolate Streptomyces sp. AM-S1 also effectively inhibited the growth of various plant and human pathogens. Further works are needed on optimization of this strain’s antagonistic activity, isolation and characterization of the antimicrobial metabolite.展开更多
Rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) has led to search of a novel bioactive compounds from natural resources. This study was aimed to determine the mode of action of bioactive compound...Rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) has led to search of a novel bioactive compounds from natural resources. This study was aimed to determine the mode of action of bioactive compounds produced by Streptomyces sp. KB1 TISTR 2304 against MRSA, including cytotoxicity against mature brine shrimp. The mode of action and cytotoxicity of bioactive compounds were performed by observing the tested MRSA cells with a scanning electron microscope and evaluated by the brine shrimp lethality bioassay, respectively. The results indicated that bioactive compounds had the mode of action at the cell wall and also showed the moderate cytotoxic activity. This study concluded that the bioactive compounds produced from strain KB1 can be used as a model for novel anti-MRSA drug development.展开更多
目的:检测miR23b和特异蛋白1(specific protein 1,Sp1)在卵巢子宫内膜异位症中的表达和分布情况,探讨二者在卵巢子宫内膜异位症发生发展中的作用及意义。方法:qPCR检测miR23b和Sp1 mRNA在异位内膜、在位内膜、正常内膜中的表达水平;免...目的:检测miR23b和特异蛋白1(specific protein 1,Sp1)在卵巢子宫内膜异位症中的表达和分布情况,探讨二者在卵巢子宫内膜异位症发生发展中的作用及意义。方法:qPCR检测miR23b和Sp1 mRNA在异位内膜、在位内膜、正常内膜中的表达水平;免疫组织化学和Western印迹检测Sp1蛋白在异位内膜、在位内膜、正常内膜的表达和分布情况。结果:MiR23b mRNA在异位内膜、在位内膜、正常内膜组中的表达水平依次增加(P<0.05)。Sp1在子宫内膜间质细胞、腺上皮细胞中均有表达,主要表达在细胞核,少量表达在胞质中;Sp1 mRNA和蛋白在异位内膜、在位内膜、正常内膜中的表达均依次降低(P<0.05)。MiR23b与Sp1 mRNA表达呈负相关(r=–0.526,P<0.05)。结论:MiR23b和Sp1与卵巢子宫内膜异位症的发生发展密切相关,二者可能通过相互拮抗,共同参与异位病灶的形成。展开更多
This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction（FGR）. The rat FGR model was est...This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction（FGR）. The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and m RNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mR NA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.展开更多
Aim： To assess whether abnormalities exist in the UBE2B gene in a population of infertile human males, and to establish biologic plausibility of any discovered mutations. Methods： We carried out polymerase chain rea...Aim： To assess whether abnormalities exist in the UBE2B gene in a population of infertile human males, and to establish biologic plausibility of any discovered mutations. Methods： We carried out polymerase chain reaction （PCR） amplification and sequence analysis of the 5＇-untranslated region and six exons of the UBE2B gene, including flanking intronic regions, in a group of fertile and infertile men. Following the identification of a putative promoter region that contained single or dual triplet deletions within a 10-CGG repeat island, we evaluated the binding affinity of these identified polymorphisms as compared to the wild-type sequence to transcription factor SP1 using a DNA-protein gel shift assay. Results： There was a novel exonic single nucleotide polymorphism （SNP） noted in exon 4 in 5% of infertile men. In silico 3D modeling of the altered protein showed an innocuous isoleucine for valine substitution. There were no mutations noted within any of the other exons. Three novel intronic SNPs were identified within the fertile group, and seven novel intronic SNPs identified in the infertile group. The DNA-protein gel shift assay noted that both single CGG deletion and double CGG deletion bands had approximately twice the binding affinity compared to the wild-type for SP1. The negative control confirmed no non-specific protein binding. Conclusion- By themselves, a single or double CGG deletion is unlikely to pose biologic significance. However, such deletions in this suspected promoter region are associated with increased binding affinity for SP1, and might represent one of several factors required for alteration of UBE2B gene expression.展开更多
Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic animals.The hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1...Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic animals.The hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1to the highly toxic exo-AFB1-8,9-epoxide(AFBO)in chicks.However,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1metabolism remains unknown.Dual-luciferase reporter assay,bioinformatics and site-directed mutation results indicated that specificity protein 1(SP1)and activator protein-1(AP-1)motifs were located in the core region-1,063/-948,-606/-541 of the CYP1A1 promoter as well as-636/-595,-503/-462,-147/-1 of the CYP2A6 promoter.Furthermore,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6.Moreover,bioactivation of AFB1to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregulation of AP-1,rather than SP1,stimulated by AFB1-induced reactive oxygen species.Additionally,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of AFB1.In conclusion,AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.展开更多
基金Supported by the China Agriculture Research System of MOF and MARA(CARS-21)the Financial Fund of the Ministry of Agriculture and Rural Affairs,China(No.NFZX2021)the National Natural Science Foundation of China(No.81973568)。
文摘A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.
文摘A new degraded sesquiterpene was isolated from the marine actinomycete Streptomyces sp. 0616208. Its structure was elucidated as （1α; 4aα; 5α, 7β, 8aβ）-5, 8a-dimethyl-decahydrona- phthalene-1, 4a, 7-triol on the basis of spectroscopic data.
文摘In the present investigation, a total number of 132 different actinomycetes strains were isolated from the humus soil samples. Out of 132 isolates, 52 showed inhibitory activity against the fungal pathogen Rhizoctonia solani. Among the antagonists, the isolate designated as AM-S1 exhibited maximum inhibitory activity against the test pathogen R. solani (41 mm). Further, the light microscopic observations of the co-cultures showed severe structural alterations in the mycelia of R. solani near the zone of inhibition. The isolate AM-S1 was identified as Streptomyces sp. by morphological and 16S rDNA sequence analysis. The color of the aerial and substrate mycelia produced by the Streptomyces sp. AM-S1 varied with different media. The isolate Streptomyces sp. AM-S1 also effectively inhibited the growth of various plant and human pathogens. Further works are needed on optimization of this strain’s antagonistic activity, isolation and characterization of the antimicrobial metabolite.
文摘Rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) has led to search of a novel bioactive compounds from natural resources. This study was aimed to determine the mode of action of bioactive compounds produced by Streptomyces sp. KB1 TISTR 2304 against MRSA, including cytotoxicity against mature brine shrimp. The mode of action and cytotoxicity of bioactive compounds were performed by observing the tested MRSA cells with a scanning electron microscope and evaluated by the brine shrimp lethality bioassay, respectively. The results indicated that bioactive compounds had the mode of action at the cell wall and also showed the moderate cytotoxic activity. This study concluded that the bioactive compounds produced from strain KB1 can be used as a model for novel anti-MRSA drug development.
基金supported by the National Natural Science Foundation of China(No.30971072)
文摘This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction（FGR）. The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and m RNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mR NA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.
文摘Aim： To assess whether abnormalities exist in the UBE2B gene in a population of infertile human males, and to establish biologic plausibility of any discovered mutations. Methods： We carried out polymerase chain reaction （PCR） amplification and sequence analysis of the 5＇-untranslated region and six exons of the UBE2B gene, including flanking intronic regions, in a group of fertile and infertile men. Following the identification of a putative promoter region that contained single or dual triplet deletions within a 10-CGG repeat island, we evaluated the binding affinity of these identified polymorphisms as compared to the wild-type sequence to transcription factor SP1 using a DNA-protein gel shift assay. Results： There was a novel exonic single nucleotide polymorphism （SNP） noted in exon 4 in 5% of infertile men. In silico 3D modeling of the altered protein showed an innocuous isoleucine for valine substitution. There were no mutations noted within any of the other exons. Three novel intronic SNPs were identified within the fertile group, and seven novel intronic SNPs identified in the infertile group. The DNA-protein gel shift assay noted that both single CGG deletion and double CGG deletion bands had approximately twice the binding affinity compared to the wild-type for SP1. The negative control confirmed no non-specific protein binding. Conclusion- By themselves, a single or double CGG deletion is unlikely to pose biologic significance. However, such deletions in this suspected promoter region are associated with increased binding affinity for SP1, and might represent one of several factors required for alteration of UBE2B gene expression.
基金partly supported by the Chinese Natural Science Foundation Projects(31772636,32072775,32272915)the National Key Research and Development Program of China(2023YFD1301003)+1 种基金the Fundamental Research Funds for the Central Universities(2662023DKPY002)the Top-notch Young Talent Supporting Program to LHS,a gift from Beijing Deyuanshun Biotechnology Co.,Ltd。
文摘Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic animals.The hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1to the highly toxic exo-AFB1-8,9-epoxide(AFBO)in chicks.However,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1metabolism remains unknown.Dual-luciferase reporter assay,bioinformatics and site-directed mutation results indicated that specificity protein 1(SP1)and activator protein-1(AP-1)motifs were located in the core region-1,063/-948,-606/-541 of the CYP1A1 promoter as well as-636/-595,-503/-462,-147/-1 of the CYP2A6 promoter.Furthermore,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6.Moreover,bioactivation of AFB1to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregulation of AP-1,rather than SP1,stimulated by AFB1-induced reactive oxygen species.Additionally,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of AFB1.In conclusion,AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.
