Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiat...Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand (all P〈0.01). Insulin-induced glucose uptake was decreased upon the activation of NOD1 (P〈0.05). NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake (all P〈0.05). Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.展开更多
Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipo...Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.展开更多
The Hongqiling large nickel-copper-cobalt deposit(hereafter referred to as the Hongqiling deposit),a typical mafic-ultramafic copper-nickel deposit in China,boasts proven Ni(Ni)resources of approximately 22×10^(4...The Hongqiling large nickel-copper-cobalt deposit(hereafter referred to as the Hongqiling deposit),a typical mafic-ultramafic copper-nickel deposit in China,boasts proven Ni(Ni)resources of approximately 22×10^(4)t,associated copper resources of 2×10^(4)t,and associated cobalt(Co)resources of 0.5×10^(4)t,with Ni reserves ranking 10th among China's magmatic nickel deposits.Geotectonically,the Hongqiling deposit is situated in the superimposed zone between the Xing'an-Mongolian orogenic belt and the circum-Western Pacific's active continental margin belt.Its ore-bearing plutons occur within the metamorphic rocks of the Ordovician Hulan Group,with the emplacement of plutons and the locations of orebodies governed by the deep-seated Huifahe fault and its secondary NW-trending Fujia-Hejiagou-Beixinglong-Changsheng fault zone.In the deposit,the rock assemblages of ore-bearing plutons predominantly encompass gabbro-pyroxenite-olivine pyroxenite-pyroxene peridotite(pluton No.1)and norite-orthopyroxenite-harzburgite(pluton No.7),with ore-bearing lithofacies consisting primarily of olivine pyroxenite and pyroxenite facies.The Hongqiling deposit hosts stratoid,overhanging lentoid,veined,and pure-sulfide veined orebodies.Its ores principally contain metallic minerals including pyrrhotite,pentlandite,chalcopyrite,violarite,and pyrite.Despite unidentified magma sources of ore-bearing mafic-ultramafic rocks,it is roughly accepted that the magmatic evolution in the Hongqiling deposit primarily involved fractional crystallization and crustal contamination.The ore-forming materials were primarily derived from the upper mantle,mixed with minor crustal materials.The ore-bearing mafic-ultramafic rocks in the deposit,primarily emplaced during the Indosinian(208-239 Ma),were formed in an intense extension setting followed by the collisional orogeny between the North China Plate and the Songnen-Zhangguangcai Range Block during the Middle-Late Triassic.From the perspective of the metallogenic geological setting,surrounding rocks,ore-controlling structures,and rock assemblages,this study identified one favorable condition and seven significant indicators for prospecting for Hongqiling-type nickel deposits and developed a prospecting model of the Hongqiling deposit.These serve as valuable references for exploring similar nickel deposits in the region,as well as the deep parts and margins of the Hongqiling deposit.展开更多
基金Supported by Grant from Department of Education of Liaoning Province(2008810)
文摘Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand (all P〈0.01). Insulin-induced glucose uptake was decreased upon the activation of NOD1 (P〈0.05). NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake (all P〈0.05). Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.
基金Supported by the Grant from the Educational Department of Liaoning Province(2008810)
文摘Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.
基金funded by projects of the China Geological Survey(Nos.DD20242070,DD20230763,DD20221695,DD20190379,and DD20160346)。
文摘The Hongqiling large nickel-copper-cobalt deposit(hereafter referred to as the Hongqiling deposit),a typical mafic-ultramafic copper-nickel deposit in China,boasts proven Ni(Ni)resources of approximately 22×10^(4)t,associated copper resources of 2×10^(4)t,and associated cobalt(Co)resources of 0.5×10^(4)t,with Ni reserves ranking 10th among China's magmatic nickel deposits.Geotectonically,the Hongqiling deposit is situated in the superimposed zone between the Xing'an-Mongolian orogenic belt and the circum-Western Pacific's active continental margin belt.Its ore-bearing plutons occur within the metamorphic rocks of the Ordovician Hulan Group,with the emplacement of plutons and the locations of orebodies governed by the deep-seated Huifahe fault and its secondary NW-trending Fujia-Hejiagou-Beixinglong-Changsheng fault zone.In the deposit,the rock assemblages of ore-bearing plutons predominantly encompass gabbro-pyroxenite-olivine pyroxenite-pyroxene peridotite(pluton No.1)and norite-orthopyroxenite-harzburgite(pluton No.7),with ore-bearing lithofacies consisting primarily of olivine pyroxenite and pyroxenite facies.The Hongqiling deposit hosts stratoid,overhanging lentoid,veined,and pure-sulfide veined orebodies.Its ores principally contain metallic minerals including pyrrhotite,pentlandite,chalcopyrite,violarite,and pyrite.Despite unidentified magma sources of ore-bearing mafic-ultramafic rocks,it is roughly accepted that the magmatic evolution in the Hongqiling deposit primarily involved fractional crystallization and crustal contamination.The ore-forming materials were primarily derived from the upper mantle,mixed with minor crustal materials.The ore-bearing mafic-ultramafic rocks in the deposit,primarily emplaced during the Indosinian(208-239 Ma),were formed in an intense extension setting followed by the collisional orogeny between the North China Plate and the Songnen-Zhangguangcai Range Block during the Middle-Late Triassic.From the perspective of the metallogenic geological setting,surrounding rocks,ore-controlling structures,and rock assemblages,this study identified one favorable condition and seven significant indicators for prospecting for Hongqiling-type nickel deposits and developed a prospecting model of the Hongqiling deposit.These serve as valuable references for exploring similar nickel deposits in the region,as well as the deep parts and margins of the Hongqiling deposit.