Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （...Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （NLRs） assemble caspase-l-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specifc and potent inhibitor of the caspase-1 pathway. Bromoxone is effective over diverse inflammatory stimuli including TLR ligands plus ATP/nigeri- cin, cytosolic DNA, flagellin and Bacillus anthracis lethal toxin. Bromoxone also efficiently suppresses easpase-1 acti- vation triggered by several types of bacterial infection. Bromoxone acts upstream or at the level of the inflammasome in a transcription-independent manner. Bromoxone also inhibits pro-IL-1β expression by targeting components up- stream of IKK in the TLR-NF-kB pathway. The unique dual activities of bromoxone are shared by the known TAK1 inhibitor that specifically blocks Nalp3 inflammasome activation. Hinted from the mechanistic and pharmacological properties of bromoxone, we further discover that several known NF-KB inhibitors that act upstream of IKK, but not those targeting IKK or IKK downstream, are potent blockers of different NLRs-mediated caspase-1 activation. Our study uncovers a possible non-transcriptional molecular link between the NLR （Nalp3）-mediated inflammasome pathway and TLR-NF-kB signaling, and suggests a potential strategy to develop new anti-inflammatory drugs.展开更多
Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done. Therefore, b...Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done. Therefore, biomarkers for early detection and new therapeutic strategies are urgently needed. miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the post-transcriptional level. miRNAs regulate proteins involved in critical cellular processes such as differentiation, proliferation, and apoptosis. Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites, including the pancreas. Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes, as well as play a role in other mechanisms of carcinogenesis. The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.展开更多
MicroRNAs are a class of small non-coding RNAs that are found in plants, animals, and some viruses. They modulate the gene function at the post-transcriptional level and act as a fine tuner of various processes, such ...MicroRNAs are a class of small non-coding RNAs that are found in plants, animals, and some viruses. They modulate the gene function at the post-transcriptional level and act as a fine tuner of various processes, such as development, proliferation, cell signaling, and apopto-sis. They are associated with different types and stages of cancer. Recent studies have shown the involvement of microRNAs in liver diseases caused by various factors, such as Hepatitis C, Hepatitis B, metabolic disorders, and by drug abuse. This review highlights the role of microRNAs in liver diseases and their potential use as therapeutic molecules.展开更多
The regulation of heat shock transcription factor to heat shock protein expression and the newest knowledge about the effect of heat shock protein on aging,immune response and the balance of cell survival and apoptosi...The regulation of heat shock transcription factor to heat shock protein expression and the newest knowledge about the effect of heat shock protein on aging,immune response and the balance of cell survival and apoptosis are summarized in the paper.展开更多
The T gene, which was cloned from the mitochondria of tumorous stem mustard （Brassica juncea var. tumida）, is a cytoplas- mic male sterility （CMS）-related gene that can produce two transcripts, T1170 and T1243. Th...The T gene, which was cloned from the mitochondria of tumorous stem mustard （Brassica juncea var. tumida）, is a cytoplas- mic male sterility （CMS）-related gene that can produce two transcripts, T1170 and T1243. The latter is transcribed with the un- cleaved intron Tinll. In our previous study, transgenic Arabidopsis thaliana plants over-expressing the T1243 transcript （OE-T1243） showed a severe male-sterile phenotype, whereas OE-Tll70 plants did not. However, the functional mechanism of the T gene in B. Juncea remained unknown. In this study, microscopic analyses of paraffin sections of anthers confirmed that OE-T1243 plants did not produce normal pollen, whereas OE-T1170 plants did. We analyzed the transcription of 15 anther development-related genes and found that transcript levels of nozzle/sporocyteless and barely any meristem 1 and 2 were markedly lower in OE-T1243 plants than those in wild type, while the transcript levels of these genes in OE-Tll70 plants were unchanged. To investigate the potential roles of TinH, we inserted the TinH sequence upstream of a minimal region （-60） of the cauliflower mosaic virus 35S promoter fused to the 5＇ end of the 13-glucuronidase （GUS） reporter gene. Analysis of the transgenic plants suggested that TinH acted as an enhancer to significantly increase GUS expression. The potential action mechanism is that the TinH intron acts as an enhancer to affect the function of the CMS-related gene T.展开更多
文摘Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （NLRs） assemble caspase-l-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specifc and potent inhibitor of the caspase-1 pathway. Bromoxone is effective over diverse inflammatory stimuli including TLR ligands plus ATP/nigeri- cin, cytosolic DNA, flagellin and Bacillus anthracis lethal toxin. Bromoxone also efficiently suppresses easpase-1 acti- vation triggered by several types of bacterial infection. Bromoxone acts upstream or at the level of the inflammasome in a transcription-independent manner. Bromoxone also inhibits pro-IL-1β expression by targeting components up- stream of IKK in the TLR-NF-kB pathway. The unique dual activities of bromoxone are shared by the known TAK1 inhibitor that specifically blocks Nalp3 inflammasome activation. Hinted from the mechanistic and pharmacological properties of bromoxone, we further discover that several known NF-KB inhibitors that act upstream of IKK, but not those targeting IKK or IKK downstream, are potent blockers of different NLRs-mediated caspase-1 activation. Our study uncovers a possible non-transcriptional molecular link between the NLR （Nalp3）-mediated inflammasome pathway and TLR-NF-kB signaling, and suggests a potential strategy to develop new anti-inflammatory drugs.
文摘Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done. Therefore, biomarkers for early detection and new therapeutic strategies are urgently needed. miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the post-transcriptional level. miRNAs regulate proteins involved in critical cellular processes such as differentiation, proliferation, and apoptosis. Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites, including the pancreas. Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes, as well as play a role in other mechanisms of carcinogenesis. The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.
基金Supported by NIH Grant AA011576-10A1 to Gyongyi Szabo and an Alfonso Martin Escudero Foundation Scholarship to Miguel Marcos
文摘MicroRNAs are a class of small non-coding RNAs that are found in plants, animals, and some viruses. They modulate the gene function at the post-transcriptional level and act as a fine tuner of various processes, such as development, proliferation, cell signaling, and apopto-sis. They are associated with different types and stages of cancer. Recent studies have shown the involvement of microRNAs in liver diseases caused by various factors, such as Hepatitis C, Hepatitis B, metabolic disorders, and by drug abuse. This review highlights the role of microRNAs in liver diseases and their potential use as therapeutic molecules.
文摘The regulation of heat shock transcription factor to heat shock protein expression and the newest knowledge about the effect of heat shock protein on aging,immune response and the balance of cell survival and apoptosis are summarized in the paper.
基金supported by the National Natural Science Foundation ofChina(31071809)to Pei YanXi
文摘The T gene, which was cloned from the mitochondria of tumorous stem mustard （Brassica juncea var. tumida）, is a cytoplas- mic male sterility （CMS）-related gene that can produce two transcripts, T1170 and T1243. The latter is transcribed with the un- cleaved intron Tinll. In our previous study, transgenic Arabidopsis thaliana plants over-expressing the T1243 transcript （OE-T1243） showed a severe male-sterile phenotype, whereas OE-Tll70 plants did not. However, the functional mechanism of the T gene in B. Juncea remained unknown. In this study, microscopic analyses of paraffin sections of anthers confirmed that OE-T1243 plants did not produce normal pollen, whereas OE-T1170 plants did. We analyzed the transcription of 15 anther development-related genes and found that transcript levels of nozzle/sporocyteless and barely any meristem 1 and 2 were markedly lower in OE-T1243 plants than those in wild type, while the transcript levels of these genes in OE-Tll70 plants were unchanged. To investigate the potential roles of TinH, we inserted the TinH sequence upstream of a minimal region （-60） of the cauliflower mosaic virus 35S promoter fused to the 5＇ end of the 13-glucuronidase （GUS） reporter gene. Analysis of the transgenic plants suggested that TinH acted as an enhancer to significantly increase GUS expression. The potential action mechanism is that the TinH intron acts as an enhancer to affect the function of the CMS-related gene T.
