Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives,setosphlides A-D(1-4),and four known analogues(5-8).Their planar s...Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives,setosphlides A-D(1-4),and four known analogues(5-8).Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods.The absolute configurations of isocoumarin nucleus for 1-4 were elucidated by their ECD spectra.The C-10 relative configurations for the pair of C-10 epimers(1 and 2)were established by comparing the magnitude of the computed 13C NMR chemical shifts(Δδcalcd.)with the experimental 13C NMR values(Δδexp.)for the epimers.All of the isolated compounds(1-8)were evaluated for their cytotoxicities against four human tumor cell lines MCF-7,MGC-803,HeLa,and Huh-7.展开更多
Gout is an independent risk factor for hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease and cerebral infarction.At present,the studies on the mechanism of gout at home and abroad have mainly focuse...Gout is an independent risk factor for hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease and cerebral infarction.At present,the studies on the mechanism of gout at home and abroad have mainly focused on immune inflammation,gene polymorphism and related studies.Uric acid deposition or crystal precipitation activates phagocytes,fibroblasts and mast cells in synovium,produces IL-1β,TNF and chemokine IL-8(CXCL8),thereby activating neutrophils,urate crystal polyanion surface can be coated with immunoglobulins and other serum proteins as substrates for complement activation,complement substitution pathways and classical complement pathways to activate complements.Uric acid crystals activate inflammation-related signal transduction pathways including the activation of inflammation-related signal transduction pathway by uric acid crystals and TLRS/MyD88 signal transduction pathways.Gene polymorphism is related to inflammation and signaling pathway,EGF gene is closely related to gout inflammation,which may be involved in the regulation of gout inflammation,among which NLRP3 inflammatory signaling pathway and gene polymorphism have been deeply studied in the pathogenesis of gout,which is the main therapeutic target of anti-inflammatory and uric acid lowering.展开更多
Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseas...Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.展开更多
Objective: microRNAs (miRNAs) are regulatory RNAs that act as important players in diverse biologic and pathologic processes. Under circumstance as podocye-injury triggering proteinuria, which miRNAs are up-regulated ...Objective: microRNAs (miRNAs) are regulatory RNAs that act as important players in diverse biologic and pathologic processes. Under circumstance as podocye-injury triggering proteinuria, which miRNAs are up-regulated or down-regulated? This experiment aims at detecting miRNAs changes in PAN nephrosis rats based on miRNA arrays and exploring the therapeutic targets of Leizhi capsule. Methods: Fifty male wistar rats were randomly divided into five groups, including control group, model group, leizhi capsule group, Tripterygium glucosides group, and valsartan group. PAN nephrosis models were made by jugular vein injection of PAN (100 mg/kg body weight, dissolve in physiological saline), while control group rats were made by jugular vein injection of physiological saline with equal volume. Other groups rats had been given medicines by irrigating stomach once a day for ten days. Blood and urine samples were collected, and renal tissues were processed after rats being euthanasised. The 24 h urinary protein excretion and blood biochemistry parameters were measured by routine methods. The glomerular morphology and podocyte ultrastructure were observed with light microscopy and transmission electron microscopy respectively. miRNA expression profile was detected by Exiqon miRNA Array. Real time RT-PCR analysis for mature miRNAs was used to validate differentially expressed miRNAs. Results: 1) In day 3 - 5, model rats had decreased urine volume, ascites, malnutrition and wight loss. From day 7 to day 10, the nephrotic syndromes were worst in model rats, but which had no skin edema. Some rats died in serious ascites, the mortality is 3/10. 2) miRNA array detection shows 106 miRNAs up regulated and 62 miRNAs down regulated in PAN nephrosis rats. Fold change (model vs. control group) varies from 1.8 to 7.0. For leizhi capsule group and model sample, there are 90 miRNAs differentially expressed, with 65 miRNAs up and 25 miRNAs down. The most important finding in our research is the discovery of the specific miRNAs related to PAN nephrosis (rno-miR23a, rno-miR-24, rno-miR-30c and rno-miR-300-3p), which have been validated by Real time RT-PCR analysis. 3) Compared with control sample, immune fluorescence intensity of dicer, expression profile of nephrin, podocin and synaptopodin mRNA and protein decrease in PAN nephrosis rats. After treated with Leizhi Capsule, immune fluorescence intensity of the above molecules improved. Conclusion: 1) Characteristic miRNAs of PAN nephrosis were screening. Up-regulated miRNAs (rno-miR-23a, rno-miR-300-3p) may trigger podocyte injury and proteinuria, while down-regulated miRNAs (rno-miR-24, rno-miR-30c) may be protective factors by anti-apoptosis. 2) Dicer and these miRNAs (rno-miR-24, rno-miR-30c, rno-miR-23a) may be are probably key molecules therapeutic targets of Leizhi capsule.展开更多
Gout has an increasing morbidity rate around the world,correlating well with hypertension,hyperlipidemia,atherosclerosis,obesity and insulin resistance,and so on.In view of Traditional Chinese Medicine(TCM),gout belon...Gout has an increasing morbidity rate around the world,correlating well with hypertension,hyperlipidemia,atherosclerosis,obesity and insulin resistance,and so on.In view of Traditional Chinese Medicine(TCM),gout belongs to arthromyodynia.Keys to syndrome differentiation of TCM are in differentiation,corporeality and coated tongue(characterized to be damp).According to the dialectical characteristics of gout TCM,this paper summarized the research of gout TCM,including food-based traditional Chinese medicine,bill of lading medicine,drug extraction,optimal herbs and dosage,individual herb and compound prescription,in order to explore and elaborate the objective curative effect and exact mechanism of gout treated by TCM.展开更多
RNase9 plays a reproductive function and has been recognized as an important member of the ribonuclease(RNase)A superfamily,a gene family that is widely used as a model for molecular evolutionary studies.Here,we ident...RNase9 plays a reproductive function and has been recognized as an important member of the ribonuclease(RNase)A superfamily,a gene family that is widely used as a model for molecular evolutionary studies.Here,we identified 178 RNase9 genes from 95 Cetartiodactyla species that represent all four lineages and 21 families of this clade.Unexpectedly,RNase9experienced an evolutionary scenario of“birth and death”in Ruminantia,and expression analyses showed that duplicated RNase9A and RNase9B genes are expressed in reproductive tissues(epididymis,vas deferens or prostate).This expression pattern combined with the estimate that these genes duplicated during the middle Eocene,a time when Ruminantia become a successful lineage,suggests that the RNase9 gene duplication might have been advantageous for promoting sperm motility and male fertility as an adaptation to climate seasonality changes of this period.In contrast,all RNase9 genes were lost in the Cetacean lineage,which might be associated with their high levels of prostatic lesions and lower reproductive rates as adaptations to a fully aquatic environment and a balance to the demands of ocean resources.This study reveals a complex and intriguing evolutionary history and functional divergence for RNase9 in Cetartiodactyla,providing new insights into the evolution of the RNaseA superfamily and molecular mechanisms for organismal adaptations to the environment.展开更多
String similarity join is an essential operation of many applications that need to find all similar string pairs from two given collections. A quantitative way to determine whether two strings are similar is to comput...String similarity join is an essential operation of many applications that need to find all similar string pairs from two given collections. A quantitative way to determine whether two strings are similar is to compute their similarity based on a certain similarity function. The string pairs with similarity above a certain threshold are regarded as results. The current approach to solving the similarity join problem is to use a unique threshold value. There are, however, several scenarios that require the support of multiple thresholds, for instance, when the dataset includes strings of various lengths. In this scenario, longer string pairs typically tolerate much more typos than shorter ones. Therefore, we proposed a so- lution for string similarity joins that supports different simi- larity thresholds in a single operator. In order to support dif- ferent thresholds, we devised two novel indexing techniques: partition based indexing and similarity aware indexing. To utilize the new indices and improve the join performance, we proposed new filtering methods and index probing tech- niques. To the best of our knowledge, this is the first work that addresses this problem. Experimental results on real-world datasets show that our solution performs efficiently while pro- viding a more flexible threshold specification.展开更多
基金This work was funded by the National Natural Science Foundation of China(31672070)National Key Research and Development Program of China(2017YFD0201400 and 2017YFD0201401)the High Performance Computer Center of Hebei University.
文摘Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives,setosphlides A-D(1-4),and four known analogues(5-8).Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods.The absolute configurations of isocoumarin nucleus for 1-4 were elucidated by their ECD spectra.The C-10 relative configurations for the pair of C-10 epimers(1 and 2)were established by comparing the magnitude of the computed 13C NMR chemical shifts(Δδcalcd.)with the experimental 13C NMR values(Δδexp.)for the epimers.All of the isolated compounds(1-8)were evaluated for their cytotoxicities against four human tumor cell lines MCF-7,MGC-803,HeLa,and Huh-7.
基金Supported by Six Peak Talents Projects in Jiangsu Province on Clinical Application of HuRAT1 Combined with ABCG2 Gene Detection in Predicting Hyperuricemia/Gout Susceptibility(2015-WSN-089)Research Projects of Traditional Chinese Medicine of Wuxi Municipal Health Commission on Mechanisms of Bixie Drink on Neutrophils and Inflammatory Signal Transduction Pathway of NLRP3 in Gout Model Rats(ZYZL201803).
文摘Gout is an independent risk factor for hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease and cerebral infarction.At present,the studies on the mechanism of gout at home and abroad have mainly focused on immune inflammation,gene polymorphism and related studies.Uric acid deposition or crystal precipitation activates phagocytes,fibroblasts and mast cells in synovium,produces IL-1β,TNF and chemokine IL-8(CXCL8),thereby activating neutrophils,urate crystal polyanion surface can be coated with immunoglobulins and other serum proteins as substrates for complement activation,complement substitution pathways and classical complement pathways to activate complements.Uric acid crystals activate inflammation-related signal transduction pathways including the activation of inflammation-related signal transduction pathway by uric acid crystals and TLRS/MyD88 signal transduction pathways.Gene polymorphism is related to inflammation and signaling pathway,EGF gene is closely related to gout inflammation,which may be involved in the regulation of gout inflammation,among which NLRP3 inflammatory signaling pathway and gene polymorphism have been deeply studied in the pathogenesis of gout,which is the main therapeutic target of anti-inflammatory and uric acid lowering.
文摘Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.
文摘Objective: microRNAs (miRNAs) are regulatory RNAs that act as important players in diverse biologic and pathologic processes. Under circumstance as podocye-injury triggering proteinuria, which miRNAs are up-regulated or down-regulated? This experiment aims at detecting miRNAs changes in PAN nephrosis rats based on miRNA arrays and exploring the therapeutic targets of Leizhi capsule. Methods: Fifty male wistar rats were randomly divided into five groups, including control group, model group, leizhi capsule group, Tripterygium glucosides group, and valsartan group. PAN nephrosis models were made by jugular vein injection of PAN (100 mg/kg body weight, dissolve in physiological saline), while control group rats were made by jugular vein injection of physiological saline with equal volume. Other groups rats had been given medicines by irrigating stomach once a day for ten days. Blood and urine samples were collected, and renal tissues were processed after rats being euthanasised. The 24 h urinary protein excretion and blood biochemistry parameters were measured by routine methods. The glomerular morphology and podocyte ultrastructure were observed with light microscopy and transmission electron microscopy respectively. miRNA expression profile was detected by Exiqon miRNA Array. Real time RT-PCR analysis for mature miRNAs was used to validate differentially expressed miRNAs. Results: 1) In day 3 - 5, model rats had decreased urine volume, ascites, malnutrition and wight loss. From day 7 to day 10, the nephrotic syndromes were worst in model rats, but which had no skin edema. Some rats died in serious ascites, the mortality is 3/10. 2) miRNA array detection shows 106 miRNAs up regulated and 62 miRNAs down regulated in PAN nephrosis rats. Fold change (model vs. control group) varies from 1.8 to 7.0. For leizhi capsule group and model sample, there are 90 miRNAs differentially expressed, with 65 miRNAs up and 25 miRNAs down. The most important finding in our research is the discovery of the specific miRNAs related to PAN nephrosis (rno-miR23a, rno-miR-24, rno-miR-30c and rno-miR-300-3p), which have been validated by Real time RT-PCR analysis. 3) Compared with control sample, immune fluorescence intensity of dicer, expression profile of nephrin, podocin and synaptopodin mRNA and protein decrease in PAN nephrosis rats. After treated with Leizhi Capsule, immune fluorescence intensity of the above molecules improved. Conclusion: 1) Characteristic miRNAs of PAN nephrosis were screening. Up-regulated miRNAs (rno-miR-23a, rno-miR-300-3p) may trigger podocyte injury and proteinuria, while down-regulated miRNAs (rno-miR-24, rno-miR-30c) may be protective factors by anti-apoptosis. 2) Dicer and these miRNAs (rno-miR-24, rno-miR-30c, rno-miR-23a) may be are probably key molecules therapeutic targets of Leizhi capsule.
基金Supported by Traditional Chinese Medicine Research Project of Wuxi Commission of Health on"Study on the Mechanism of Bi Xie Yin on Neutrophils and Inflammatory Signal Transduction Pathway of NLRP3 in Gout Model Rats"(Project No.:ZYZL201803)Six Talent Peaks Project in Jiangsu Province on Clinical Application of huRAT1 Combined with ABCG2 Gene Detection in Predicting Hyperuricemia/Gout Susceptibility(Project No.:2015-WSN-089)
文摘Gout has an increasing morbidity rate around the world,correlating well with hypertension,hyperlipidemia,atherosclerosis,obesity and insulin resistance,and so on.In view of Traditional Chinese Medicine(TCM),gout belongs to arthromyodynia.Keys to syndrome differentiation of TCM are in differentiation,corporeality and coated tongue(characterized to be damp).According to the dialectical characteristics of gout TCM,this paper summarized the research of gout TCM,including food-based traditional Chinese medicine,bill of lading medicine,drug extraction,optimal herbs and dosage,individual herb and compound prescription,in order to explore and elaborate the objective curative effect and exact mechanism of gout treated by TCM.
基金supported by the Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities(202001AO070195)the National Natural Science Foundation of China(31925006)the Applied Basic Research General Project of Yunnan Science Technology Department(202001BB050058)。
文摘RNase9 plays a reproductive function and has been recognized as an important member of the ribonuclease(RNase)A superfamily,a gene family that is widely used as a model for molecular evolutionary studies.Here,we identified 178 RNase9 genes from 95 Cetartiodactyla species that represent all four lineages and 21 families of this clade.Unexpectedly,RNase9experienced an evolutionary scenario of“birth and death”in Ruminantia,and expression analyses showed that duplicated RNase9A and RNase9B genes are expressed in reproductive tissues(epididymis,vas deferens or prostate).This expression pattern combined with the estimate that these genes duplicated during the middle Eocene,a time when Ruminantia become a successful lineage,suggests that the RNase9 gene duplication might have been advantageous for promoting sperm motility and male fertility as an adaptation to climate seasonality changes of this period.In contrast,all RNase9 genes were lost in the Cetacean lineage,which might be associated with their high levels of prostatic lesions and lower reproductive rates as adaptations to a fully aquatic environment and a balance to the demands of ocean resources.This study reveals a complex and intriguing evolutionary history and functional divergence for RNase9 in Cetartiodactyla,providing new insights into the evolution of the RNaseA superfamily and molecular mechanisms for organismal adaptations to the environment.
基金This work was supported by China Scholarship Council and the National Natural Science Foundation of China (Grant Nos. 61402329 and 51378350).
文摘String similarity join is an essential operation of many applications that need to find all similar string pairs from two given collections. A quantitative way to determine whether two strings are similar is to compute their similarity based on a certain similarity function. The string pairs with similarity above a certain threshold are regarded as results. The current approach to solving the similarity join problem is to use a unique threshold value. There are, however, several scenarios that require the support of multiple thresholds, for instance, when the dataset includes strings of various lengths. In this scenario, longer string pairs typically tolerate much more typos than shorter ones. Therefore, we proposed a so- lution for string similarity joins that supports different simi- larity thresholds in a single operator. In order to support dif- ferent thresholds, we devised two novel indexing techniques: partition based indexing and similarity aware indexing. To utilize the new indices and improve the join performance, we proposed new filtering methods and index probing tech- niques. To the best of our knowledge, this is the first work that addresses this problem. Experimental results on real-world datasets show that our solution performs efficiently while pro- viding a more flexible threshold specification.