AIM: To investigate the role of key iron-regulatory protein, hepcidin in non-alcoholic fatty liver disease(NAFLD). METHODS: Hepcidin(Hamp1) knockout and floxed control mice were administered a high fat and high sucros...AIM: To investigate the role of key iron-regulatory protein, hepcidin in non-alcoholic fatty liver disease(NAFLD). METHODS: Hepcidin(Hamp1) knockout and floxed control mice were administered a high fat and high sucrose(HFS) or a regular control diet for 3 or 7 mo. Steatosis, triglycerides, fibrosis, protein and gene expression in mice livers were determined by histological and biochemical techniques, western blotting and realtime polymerase chain reaction. RESULTS: Knockout mice exhibited hepatic iron accumulation. Despite similar weight gains, HFS feeding induced hepatomegaly in floxed, but not knockout, mice. The livers of floxed mice exhibited higher levels of steatosis, triglycerides and c-Jun N-terminal kinase(JNK) phosphorylation than knockout mice. In contrast, a significant increase in fibrosis was observed in knockout mice livers within 3 mo of HFS administration. The hepatic gene expression levels of sterol regulatoryelement-binding protein-1c and fat-specific protein-27, but not peroxisome proliferator-activated receptoralpha or microsomal triglyceride transfer protein, were attenuated in HFS-fed knockout mice. Knockout mice fed with regular diet displayed increased carnitine palmitoyltransferase-1a and phosphoenolpyruvate carboxykinase-1 but decreased glucose-6-phosphatase expression in the liver. In summary, attenuated steatosis correlated with decreased expression of lipogenic and lipid storage genes, and JNK phosphorylation. Deletion of Hamp1 alleles per se modulated hepatic expression of beta-oxidation and gluconeogenic genes. CONCLUSION: Lack of hepcidin expression inhibits hepatic lipid accumulation and induces early development of fibrosis following high fat intake. Hepcidin and iron may play a role in the regulation of metabolic pathways in the liver, which has implications for NAFLD pathogenesis.展开更多
Soils are not exempt from anthropogenic pollution,which can eventually cause disturbance of the microbial communities and areas without any kind of productivity.Among soil microbiota,bacteria play an important role in...Soils are not exempt from anthropogenic pollution,which can eventually cause disturbance of the microbial communities and areas without any kind of productivity.Among soil microbiota,bacteria play an important role in pollutant degradation,enabling them to thrive in contaminated sites.Given this,several techniques have been used to increase the number of pollutantdegrading bacteria in situ or for subsequent addition.Additionally,bacteriophages exhibit a high tolerance to pollutants and enhance bacterial metabolic activity through phage-encoded auxiliary metabolic genes(AMGs),thereby augmenting their skills for nutrient assimilation,resistance to phage infection,antibiotic resistance,heavy metal resistance,and degradation of pesticides and xenobiotics,among others.Several phage-encoded AMGs have been described during the last few years,but their diversity,distribution,and function have not been extensively explored,warranting further studies.Here,we highlight soil microbiome interactions,especially bacterium and phage interactions to understand this unexplored world with a high potential for restoring polluted soils.展开更多
目的:通过生物信息学方法分析乳腺癌的关键代谢基因并进行生存预后分析。方法:通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库获取乳腺癌转录组数据,利用GSEA数据库查找相关代谢基因,匹配TCGA数据库相关基因,明确最终代谢基因...目的:通过生物信息学方法分析乳腺癌的关键代谢基因并进行生存预后分析。方法:通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库获取乳腺癌转录组数据,利用GSEA数据库查找相关代谢基因,匹配TCGA数据库相关基因,明确最终代谢基因;利用Lasso模型构建,得出生存预后分析结果。结果:得到了3个与乳腺癌相关的代谢基因,分别为POLR2K、NMNAT2、SUCLA2。生存分析结果显示高风险组和低风险组最长生存时间均为24年,年龄、状态、肿瘤分期这3个因素可作为单因素的独立预后。结论:POLR2K基因是最为明显的高表达基因,且初步显示该基因与乳腺癌的发生、发展及预后存在一定相关性,但需要通过实验验证来确认。展开更多
代谢综合征(metabolic syndrome,MS)是一组复杂的代谢紊乱疾病,近年其逐渐成为对居民健康影响较大的公共卫生问题。MS的发生是由遗传和环境因素共同作用导致的,其遗传异质性和表型异质性强,许多基因及其多态性都与MS或其组分的发生有关...代谢综合征(metabolic syndrome,MS)是一组复杂的代谢紊乱疾病,近年其逐渐成为对居民健康影响较大的公共卫生问题。MS的发生是由遗传和环境因素共同作用导致的,其遗传异质性和表型异质性强,许多基因及其多态性都与MS或其组分的发生有关。有关MS及其组分相关基因多态性的研究主要集中在脂联素编码基因(ADIPOQ)、过氧化物酶体增殖物激活受体γ基因(PPARγ)、转录因子7类似物2基因(TCF7L2)、脂肪含量和肥胖相关基因(fat mass and obesity-associated gene,FTO)和载脂蛋白基因等。而目前针对女性的遗传研究尚未引起广泛关注,尚需进一步研究以寻找其致病的特异性基因,为改善女性健康提供帮助。综述近年MS相关的基因多态性的研究热点。展开更多
AIM:To investigate the roles of the ribonucleotide reductase M2 (RRM2) subunit in colorectal cancer (CRC) and ultraviolet (UV)-induced DNA damage repair. METHODS:Immunohistochemical staining of tissue microarray was p...AIM:To investigate the roles of the ribonucleotide reductase M2 (RRM2) subunit in colorectal cancer (CRC) and ultraviolet (UV)-induced DNA damage repair. METHODS:Immunohistochemical staining of tissue microarray was performed to detect the expression of RRM2. Seven CRC cell lines were cultured and three human colon cancer cell lines, i.e., HCT116, SW480 and SW620, were used. Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of RRM2, respectively. Cell proliferation assay, cell cycle analysis were performed. Cell apoptosis was evaluated by double staining with fluorescein isothiocyanate-conjugated Annexin Ⅴ and propidium iodide (PI) usingAnnexin Ⅴ/PI apoptosis kit. The motility and invasion of CRC cells were assessed by the Transwell chamber assay. Cells were irradiated with a 254 nm UV-C lamp to detect the UV sensitivity after RRM2 depletion. RESULTS:Immunohistochemical staining revealed elevated RRM2 levels in CRC tissues. RRM2 overexpression was positively correlated with invasion depth (P < 0.05), poorly differentiated type (P = 0.0051), and tumor node metastasis stage (P = 0.0015). The expression of RRM2 in HCT116 cells was downregulated after transfection, and HCT116 cell proliferation was obviously suppressed compared to control groups (P < 0.05). In the invasion test, the number of cells that passed through the chambers in the RRM2-siRNA group was 81 ± 3, which was lower than that in the negative control (289 ± 7) and blank control groups (301 ± 7.2). These differences were statistically significant (P < 0.01). Our data suggest that RRM2 overexpression may be associated with CRC progression. RRM2 silencing by siRNA may inhibit the hyperplasia and invasiveness of CRC cells, suggesting that RRM2 may play an important role in the infiltration and metastasis of CRC, which is a potential therapeutic strategy in CRC. In addition, RRM2 depletion increased UV sensitivity. CONCLUSION:These findings suggest that RRM2 may be 展开更多
基金NIH grant No.R01AA017738(to Harrison-Findik DD)University of Nebraska Medical Center Graduate Assistantship/Fellowship(to Lu S)
文摘AIM: To investigate the role of key iron-regulatory protein, hepcidin in non-alcoholic fatty liver disease(NAFLD). METHODS: Hepcidin(Hamp1) knockout and floxed control mice were administered a high fat and high sucrose(HFS) or a regular control diet for 3 or 7 mo. Steatosis, triglycerides, fibrosis, protein and gene expression in mice livers were determined by histological and biochemical techniques, western blotting and realtime polymerase chain reaction. RESULTS: Knockout mice exhibited hepatic iron accumulation. Despite similar weight gains, HFS feeding induced hepatomegaly in floxed, but not knockout, mice. The livers of floxed mice exhibited higher levels of steatosis, triglycerides and c-Jun N-terminal kinase(JNK) phosphorylation than knockout mice. In contrast, a significant increase in fibrosis was observed in knockout mice livers within 3 mo of HFS administration. The hepatic gene expression levels of sterol regulatoryelement-binding protein-1c and fat-specific protein-27, but not peroxisome proliferator-activated receptoralpha or microsomal triglyceride transfer protein, were attenuated in HFS-fed knockout mice. Knockout mice fed with regular diet displayed increased carnitine palmitoyltransferase-1a and phosphoenolpyruvate carboxykinase-1 but decreased glucose-6-phosphatase expression in the liver. In summary, attenuated steatosis correlated with decreased expression of lipogenic and lipid storage genes, and JNK phosphorylation. Deletion of Hamp1 alleles per se modulated hepatic expression of beta-oxidation and gluconeogenic genes. CONCLUSION: Lack of hepcidin expression inhibits hepatic lipid accumulation and induces early development of fibrosis following high fat intake. Hepcidin and iron may play a role in the regulation of metabolic pathways in the liver, which has implications for NAFLD pathogenesis.
基金the European Union’s Horizon Europe 2020 Research and Innovation Program under the Marie Skłodowska-Curie(No.101106707)Generalitat de Catalunya through Consolidated Research Group 2021 SGR 01282 and from the CERCA program.
文摘Soils are not exempt from anthropogenic pollution,which can eventually cause disturbance of the microbial communities and areas without any kind of productivity.Among soil microbiota,bacteria play an important role in pollutant degradation,enabling them to thrive in contaminated sites.Given this,several techniques have been used to increase the number of pollutantdegrading bacteria in situ or for subsequent addition.Additionally,bacteriophages exhibit a high tolerance to pollutants and enhance bacterial metabolic activity through phage-encoded auxiliary metabolic genes(AMGs),thereby augmenting their skills for nutrient assimilation,resistance to phage infection,antibiotic resistance,heavy metal resistance,and degradation of pesticides and xenobiotics,among others.Several phage-encoded AMGs have been described during the last few years,but their diversity,distribution,and function have not been extensively explored,warranting further studies.Here,we highlight soil microbiome interactions,especially bacterium and phage interactions to understand this unexplored world with a high potential for restoring polluted soils.
文摘目的:通过生物信息学方法分析乳腺癌的关键代谢基因并进行生存预后分析。方法:通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库获取乳腺癌转录组数据,利用GSEA数据库查找相关代谢基因,匹配TCGA数据库相关基因,明确最终代谢基因;利用Lasso模型构建,得出生存预后分析结果。结果:得到了3个与乳腺癌相关的代谢基因,分别为POLR2K、NMNAT2、SUCLA2。生存分析结果显示高风险组和低风险组最长生存时间均为24年,年龄、状态、肿瘤分期这3个因素可作为单因素的独立预后。结论:POLR2K基因是最为明显的高表达基因,且初步显示该基因与乳腺癌的发生、发展及预后存在一定相关性,但需要通过实验验证来确认。
文摘[目的]通过研究套种对浙贝母根际土壤细菌结构及功能基因的作用,探讨其改善浙贝母连作障碍的微生态机制。[方法]采用田间试验,将浙贝母与不同作物套种,利用Miseq测序及基于16S rRNA扩增子测序结果预测微生物群落(Phylogenetic Investigationof Communities by Reconstruction of Unobserved States,PICRUSt)功能分析解析浙贝母根际细菌群落结构及功能基因结构的组成差异。[结果]浙贝母与其他作物套种后,根际细菌的结构和多样性发生了明显改变。与单种浙贝相比,套种提高了根际细菌的多样性,其中浮霉菌门、酸杆菌门、放线菌门相对丰度显著上升。在属水平上,酸杆菌门的GP1属、GP2属、浮霉菌门的副球菌属以及放线菌门的放线菌属相对丰度明显升高,且生姜套种组中GP1属、GP2属以及副球菌属均为最高水平。细菌功能差异分析表明,套种提高了细胞壁/膜内源物质合成、次级代谢产物合成/转运/代谢、无机离子转运代谢以及防御机制4个方面功能基因丰度,而生姜套种组中这4个方面功能基因丰度最高。[结论]套种通过提高浙贝根际土壤细菌多样性,增加了生长促进细菌以及生防菌的含量,提高了浙贝产量以及药效成分含量。从微生态角度来说,浙贝母与生姜套种是最有利的方式。
文摘代谢综合征(metabolic syndrome,MS)是一组复杂的代谢紊乱疾病,近年其逐渐成为对居民健康影响较大的公共卫生问题。MS的发生是由遗传和环境因素共同作用导致的,其遗传异质性和表型异质性强,许多基因及其多态性都与MS或其组分的发生有关。有关MS及其组分相关基因多态性的研究主要集中在脂联素编码基因(ADIPOQ)、过氧化物酶体增殖物激活受体γ基因(PPARγ)、转录因子7类似物2基因(TCF7L2)、脂肪含量和肥胖相关基因(fat mass and obesity-associated gene,FTO)和载脂蛋白基因等。而目前针对女性的遗传研究尚未引起广泛关注,尚需进一步研究以寻找其致病的特异性基因,为改善女性健康提供帮助。综述近年MS相关的基因多态性的研究热点。
文摘AIM:To investigate the roles of the ribonucleotide reductase M2 (RRM2) subunit in colorectal cancer (CRC) and ultraviolet (UV)-induced DNA damage repair. METHODS:Immunohistochemical staining of tissue microarray was performed to detect the expression of RRM2. Seven CRC cell lines were cultured and three human colon cancer cell lines, i.e., HCT116, SW480 and SW620, were used. Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of RRM2, respectively. Cell proliferation assay, cell cycle analysis were performed. Cell apoptosis was evaluated by double staining with fluorescein isothiocyanate-conjugated Annexin Ⅴ and propidium iodide (PI) usingAnnexin Ⅴ/PI apoptosis kit. The motility and invasion of CRC cells were assessed by the Transwell chamber assay. Cells were irradiated with a 254 nm UV-C lamp to detect the UV sensitivity after RRM2 depletion. RESULTS:Immunohistochemical staining revealed elevated RRM2 levels in CRC tissues. RRM2 overexpression was positively correlated with invasion depth (P < 0.05), poorly differentiated type (P = 0.0051), and tumor node metastasis stage (P = 0.0015). The expression of RRM2 in HCT116 cells was downregulated after transfection, and HCT116 cell proliferation was obviously suppressed compared to control groups (P < 0.05). In the invasion test, the number of cells that passed through the chambers in the RRM2-siRNA group was 81 ± 3, which was lower than that in the negative control (289 ± 7) and blank control groups (301 ± 7.2). These differences were statistically significant (P < 0.01). Our data suggest that RRM2 overexpression may be associated with CRC progression. RRM2 silencing by siRNA may inhibit the hyperplasia and invasiveness of CRC cells, suggesting that RRM2 may play an important role in the infiltration and metastasis of CRC, which is a potential therapeutic strategy in CRC. In addition, RRM2 depletion increased UV sensitivity. CONCLUSION:These findings suggest that RRM2 may be
