Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect...Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.展开更多
Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligon...Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus in Lep△I14/△I14）and wild-type（WT） rats. We found 1,651 differentially expressed（enriched） genes in white adipose tissue,916 in the liver, and 306 in the hypothalamus in the Lep△I14/△I14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.展开更多
AIM: To establish the DNA methylation patterns of the promoter CpG islands of 14 'drug-resistance' genes in hepatocellular carcinoma (HCC).METHODS: The methylation specific polymerase chain reaction in conjunc...AIM: To establish the DNA methylation patterns of the promoter CpG islands of 14 'drug-resistance' genes in hepatocellular carcinoma (HCC).METHODS: The methylation specific polymerase chain reaction in conjunction with sequencing verification was used to establish the methylation patterns of the 14 genes in the liver tissues of four healthy liver donors, as well as tumor and the paired non-cancerous tissues of 30 HCC patients.RESULTS: While 11 genes (ATP-binding cassette, sub-family G (WHITE), member 2(ABCG2), activating transcription factor (ATF2), beta-2-microglobulin (B2M), deoxycytidine kinase(DCK, occludin (OCLN, v-raf-1 murine leukemia viral oncogene homolog (RAF/), ralA binding protein 1 (RALBP1),splicing factor (45 kD) (SPF45), S-phase kinase-associated protein 2 (p45) (SKP2), tumor protein p53 (Li-Fraumeni syndrome) (TP53) and topoisomerase (DNA) II beta (TOP2B) maintained the unmethylated patterns, three genes displayed to various extents the hypermethylation state in tumor tissues in comparison with the normal counterparts. The catalase (CAT) was hypermethylated in tumor and the neighboring non-cancerous tissue of one case (3.3%). Both glutathione S-transferase pi (GSTp/) (80%, 24/30 in tumor and 56.7%,17/30 in the paired non-cancerous tissues) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) (CF-FR) (77%, 23/30 in tumor and 50%, 15/30 in the paired non-cancerous tissues) genes were prevalently hypermethylated in HCC as well as their neighboring non-cancerous tissues. No significant difference in the hypermethylation occurrence was observed between the HCC and its neighboring non-cancerous tissues.CONCLUSION: Hypermethylation of promoter CpG islands of both CF-FR and GSTpigenes occurs prevalently in HCC,which may correlate with the low expression of these two genes at the mRNA level and has the profound etiological and clinical implications. It is likely to be specific to the early phase of HCC carcinogenesis.展开更多
Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data...Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.展开更多
Objective: To study the relationship between 14-3-3 sigma gene promoter hypermethylation and its transcrip-tion levels in sporadic breast carcinogenesis. Methods: Hypermethylation of 14-3-3 sigma gene was detected by ...Objective: To study the relationship between 14-3-3 sigma gene promoter hypermethylation and its transcrip-tion levels in sporadic breast carcinogenesis. Methods: Hypermethylation of 14-3-3 sigma gene was detected by sensitive MSP assay in carcinous, non-cancerious and normal tissue, and its mRNA was also detected by real-time PCR based on SYBR Green 1. Results: The hypermethylation frequencies of 14-3-3 sigma were 90% in 68 cases of sporadic breast cancer patients. Hypermethylation was presented in portions (2/13,18%) of hyperplastic samples, and no hypermethylation was presented in normal tissue. The hypermethylation change of 14-3-3 sigma gene was markedly related with various types, grades and lymph node metastases (P < 0.05), and no significant differences in methylation frequencies were seen between premenopause and postmenopause (P > 0.05). The hypermethylation of 14-3-3 sigma showed reverse relationship with its mRNA transcription (P < 0.05). Only lymph node metastases was strongly associated with poor outcome (P = 0.02). Whether 14-3-3 sigma promoter methylation or not did not affect the 5-year survival rate of sporadic breast cancer (P > 0.05). Conclu-sion: Epigenetics alterations of the 14-3-3 sigma can contribute to reducing or losing the expression of 14-3-3 sigma protein, which plays an important role in the development of sporadic breast carcinomas including various types, grades and lymph node metastases.展开更多
In this study area the geological conditions are complicated and the effective sandstone is very heterogeneous.The sandstones are thin and lateral and vertical variations are large.We introduce multi-attribute fusion ...In this study area the geological conditions are complicated and the effective sandstone is very heterogeneous.The sandstones are thin and lateral and vertical variations are large.We introduce multi-attribute fusion technology based on pre-stack seismic data, pre-stack P-and S-wave inversion results,and post-stack attributes.This method not only can keep the fluid information contained in pre-stack seismic data but also make use of the high SNR characteristics of post-stack data.First,we use a one-step recursive method to get the optimal attribute combination from a number of attributes.Second,we use a probabilistic neural network method to train the nonlinear relationship between log curves and seismic attributes and then use the trained samples to find the natural gamma ray distribution in the Su-14 well block and improve the resolution of seismic data.Finally,we predict the effective reservoir distribution in the Su-14 well block.展开更多
[ Objective] The aim was to observe the ultrastructure of different callus structures in Heiya No. 14 by transmission electron microscopy. [Methods] Sample preparation and observation were both carried out by conventi...[ Objective] The aim was to observe the ultrastructure of different callus structures in Heiya No. 14 by transmission electron microscopy. [Methods] Sample preparation and observation were both carried out by conventional transmission electron microscopy. [ Results] It was showed by transmission electron microscopy that the initial callus cells had a large central vacuole, which squeezed its cytoplasm to be a thin layer around the brim of cell, Meanwhile the nuclear was also squeezed to distribute in the corner of cell, but its nucleolus could be still observed; Compared embryogenic callus with initial callus, its cell wall became thick, and many starch grains and chloroplasts including starch grains could be observed in the cytoplasm area of cell membrane; In non-embryoenic callus, no organelles except for the vacuole could be observed; In browning callus, there was almost no organelles in cells. [ Conclusion] There are significant differences in different types of flax callus at the cell ultrastructure level, which can be as an index for reflecting the differentiation ability of callus cell.展开更多
基金Grant support was received from the National Natural Science Foundation of China(32072182).
文摘Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.
基金supported by grants from the National Natural Science Foundation of China (No. 81470150)
文摘Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus in Lep△I14/△I14）and wild-type（WT） rats. We found 1,651 differentially expressed（enriched） genes in white adipose tissue,916 in the liver, and 306 in the hypothalamus in the Lep△I14/△I14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.
基金Supported by the National High Technology Research and Development Program of China (863 program),No.2002AA2Z3353 and the Science Foundation of Shanghai Municipal Government,No.02DJ14056
文摘AIM: To establish the DNA methylation patterns of the promoter CpG islands of 14 'drug-resistance' genes in hepatocellular carcinoma (HCC).METHODS: The methylation specific polymerase chain reaction in conjunction with sequencing verification was used to establish the methylation patterns of the 14 genes in the liver tissues of four healthy liver donors, as well as tumor and the paired non-cancerous tissues of 30 HCC patients.RESULTS: While 11 genes (ATP-binding cassette, sub-family G (WHITE), member 2(ABCG2), activating transcription factor (ATF2), beta-2-microglobulin (B2M), deoxycytidine kinase(DCK, occludin (OCLN, v-raf-1 murine leukemia viral oncogene homolog (RAF/), ralA binding protein 1 (RALBP1),splicing factor (45 kD) (SPF45), S-phase kinase-associated protein 2 (p45) (SKP2), tumor protein p53 (Li-Fraumeni syndrome) (TP53) and topoisomerase (DNA) II beta (TOP2B) maintained the unmethylated patterns, three genes displayed to various extents the hypermethylation state in tumor tissues in comparison with the normal counterparts. The catalase (CAT) was hypermethylated in tumor and the neighboring non-cancerous tissue of one case (3.3%). Both glutathione S-transferase pi (GSTp/) (80%, 24/30 in tumor and 56.7%,17/30 in the paired non-cancerous tissues) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) (CF-FR) (77%, 23/30 in tumor and 50%, 15/30 in the paired non-cancerous tissues) genes were prevalently hypermethylated in HCC as well as their neighboring non-cancerous tissues. No significant difference in the hypermethylation occurrence was observed between the HCC and its neighboring non-cancerous tissues.CONCLUSION: Hypermethylation of promoter CpG islands of both CF-FR and GSTpigenes occurs prevalently in HCC,which may correlate with the low expression of these two genes at the mRNA level and has the profound etiological and clinical implications. It is likely to be specific to the early phase of HCC carcinogenesis.
基金supported by the National Innovation and Enterpreneurship Training Program for College Students(202210367002)the Key Laboratory Open Project of An-hui Province(AHCM2022Z004).
文摘Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.
基金Supported by a grant from the Natural Sciences Foundation of Hubei Province (No. 2007ABA371).
文摘Objective: To study the relationship between 14-3-3 sigma gene promoter hypermethylation and its transcrip-tion levels in sporadic breast carcinogenesis. Methods: Hypermethylation of 14-3-3 sigma gene was detected by sensitive MSP assay in carcinous, non-cancerious and normal tissue, and its mRNA was also detected by real-time PCR based on SYBR Green 1. Results: The hypermethylation frequencies of 14-3-3 sigma were 90% in 68 cases of sporadic breast cancer patients. Hypermethylation was presented in portions (2/13,18%) of hyperplastic samples, and no hypermethylation was presented in normal tissue. The hypermethylation change of 14-3-3 sigma gene was markedly related with various types, grades and lymph node metastases (P < 0.05), and no significant differences in methylation frequencies were seen between premenopause and postmenopause (P > 0.05). The hypermethylation of 14-3-3 sigma showed reverse relationship with its mRNA transcription (P < 0.05). Only lymph node metastases was strongly associated with poor outcome (P = 0.02). Whether 14-3-3 sigma promoter methylation or not did not affect the 5-year survival rate of sporadic breast cancer (P > 0.05). Conclu-sion: Epigenetics alterations of the 14-3-3 sigma can contribute to reducing or losing the expression of 14-3-3 sigma protein, which plays an important role in the development of sporadic breast carcinomas including various types, grades and lymph node metastases.
基金The National Natural Science Foundation of China and China Petroleum&Chemical Corporation Co-funded Project(Grant Nos 40839905 and 40739907)
文摘In this study area the geological conditions are complicated and the effective sandstone is very heterogeneous.The sandstones are thin and lateral and vertical variations are large.We introduce multi-attribute fusion technology based on pre-stack seismic data, pre-stack P-and S-wave inversion results,and post-stack attributes.This method not only can keep the fluid information contained in pre-stack seismic data but also make use of the high SNR characteristics of post-stack data.First,we use a one-step recursive method to get the optimal attribute combination from a number of attributes.Second,we use a probabilistic neural network method to train the nonlinear relationship between log curves and seismic attributes and then use the trained samples to find the natural gamma ray distribution in the Su-14 well block and improve the resolution of seismic data.Finally,we predict the effective reservoir distribution in the Su-14 well block.
基金Supported by Harbin Postdoctoral Foundation(LRB08-491)~~
文摘[ Objective] The aim was to observe the ultrastructure of different callus structures in Heiya No. 14 by transmission electron microscopy. [Methods] Sample preparation and observation were both carried out by conventional transmission electron microscopy. [ Results] It was showed by transmission electron microscopy that the initial callus cells had a large central vacuole, which squeezed its cytoplasm to be a thin layer around the brim of cell, Meanwhile the nuclear was also squeezed to distribute in the corner of cell, but its nucleolus could be still observed; Compared embryogenic callus with initial callus, its cell wall became thick, and many starch grains and chloroplasts including starch grains could be observed in the cytoplasm area of cell membrane; In non-embryoenic callus, no organelles except for the vacuole could be observed; In browning callus, there was almost no organelles in cells. [ Conclusion] There are significant differences in different types of flax callus at the cell ultrastructure level, which can be as an index for reflecting the differentiation ability of callus cell.
