While migration is widely recognized as a valid option for improving farmers’ income, the welfare effects of migration on left-behind family members are ambiguous. This study examines the impacts of migration on left...While migration is widely recognized as a valid option for improving farmers’ income, the welfare effects of migration on left-behind family members are ambiguous. This study examines the impacts of migration on left-behind family members’ food consumption and nutrient intake, particularly in remote rural areas in China. Based on household survey data collected from 611 smallholder rubber farmers in Xishuangbanna Dai Autonomous Prefecture of southwestern China, the empirical results suggest that the migration of family members contributes to improving household net income, whereas it negatively affects left-behind family members’ consumption of grain and pork. Migration also leads to a decrease in left-behind family members’ nutrient intake. Surprisingly, the economic returns of farmers’ migration not only do not foster the transformation of household food consumption from a staple food-dominated dietary structure to one including more meat and dairy products but also reduce left-behind family members’ nutrient intake. This study adds to the literature on the impact of farmers’ migration. The findings have important implications for better understanding the impacts of migration on farmers’ livelihood and human capital development in rural China.展开更多
AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochem...AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples.RESULTS: IL-8 and CXCR1 proteins were both overexpressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.展开更多
AIM: To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC. METHODS: FAP expression was examined in 134 ...AIM: To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC. METHODS: FAP expression was examined in 134 PDAC specimens by immunohistochemistry, and in four pancreatic cancer cell lines (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also analyzed the association between FAP expression in PDAC cells and the clinicopathology of PDAC patients. RESULTS: The results showed that the FAP was expressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at different levels. Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its88-kDa seprase subunit were identif ied. Higher FAP expression in carcinoma cells was associated with tumor size (P < 0.001), fi brotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical outcome (P = 0.0085). CONCLUSION: FAP is highly expressed in carcinoma cells and f ibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.展开更多
We used cDNA microarrays containing ~9,000 unigenes to identify 486 salt responsive expressed sequence tags (ESTs) (representing ~450 unigenes) in shoots of the highly salt-tolerant rice variety, Nona Bokra (Oryza s...We used cDNA microarrays containing ~9,000 unigenes to identify 486 salt responsive expressed sequence tags (ESTs) (representing ~450 unigenes) in shoots of the highly salt-tolerant rice variety, Nona Bokra (Oryza sativa L. Ssp.Indica pv. Nona). Some of the genes identified in this study had previously been associated with salt stress. Howeverthe majority were novel, indicating that there is a great number of genes that are induced by salt exposure. Analysis of the salt stress expression profile data of Nona provided clues regarding some putative cellular and molecular processes that are undertaken by this tolerant rice variety in response to salt stress. Namely, we found that multiple transcription factors were induced during the initial salt response of shoots. Many genes whose encoded proteins are implicated in detoxification, protectant and transport were rapidly induced. Genes supporting photosynthesis were repressed and those supporting carbohydrate metabolism were altered. Commonality among the genes induced by salt exposure with those induced during senescence and biotic stress responses suggests that there are shared signaling pathways among these processes. We further compared the transcriptome changes of the salt-sensitive cultivar, IR28, with that of Nona rice. Many genes that are salt responsive in Nona were found to be differentially regulated in IR28. This study identified a large number of candidate functional genes that appear to be involved in salt tolerance and further examination of these genes may enable the molecular basis of salt tolerance to be elucidated.展开更多
AIM: To explore the effect of the histone deacetylase inhibitor givinostat on proteins related to regulation of hepatic stellate cell proliferation.METHODS: The cell counting kit-8 assay and flow cytometry were used t...AIM: To explore the effect of the histone deacetylase inhibitor givinostat on proteins related to regulation of hepatic stellate cell proliferation.METHODS: The cell counting kit-8 assay and flow cytometry were used to observe changes in proliferation, apoptosis, and cell cycle in hepatic stellate cells treated with givinostat. Western blot was used to observe expression changes in p21, p57, CDK4, CDK6, cyclin D1, caspase-3, and caspase-9 in hepatic stellate cells exposed to givinostat. The scratch assay was used to analyze the effect of givinostat on cell migration. Effects of givinostat on the reactive oxygen species profile, mitochondrial membrane potential, and mitochondrial permeability transition pore opening in JS-1 cells were observed by laser confocal microscopy.RESULTS: Givinostat significantly inhibited JS-1 cell proliferation and promoted cell apoptosis, leading to cell cycle arrest in G0/G1 phases. Treatment with givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas expression of p21 and p57 was significantly increased. The givinostat-induced apoptosis of hepatic stellate cells was mainly mediatedthrough p38 and extracellular signal-regulated kinase 1/2. Givinostat treatment increased intracellular reactive oxygen species production, decreased mitochondrial membrane potential, and promoted mitochondrial permeability transition pore opening. Acetylation of superoxide dismutase(acetyl K68) and nuclear factor-κB p65(acetyl K310) was upregulated, while there was no change in protein expression. Moreover, the notable beneficial effect of givinostat on liver fibrosis was also confirmed in the mouse models.CONCLUSION: Givinostat has antifibrotic activities via regulating the acetylation of nuclear factor-κB and superoxide dismutase 2, thus inhibiting hepatic stellate cell proliferation and inducing apoptosis.展开更多
This study assesses the impacts of the COVID-19 pandemic on Chinese residents’food safety knowledge and behavior,and explores the possible influence mechanism,namely,focus on media information.The study is based on i...This study assesses the impacts of the COVID-19 pandemic on Chinese residents’food safety knowledge and behavior,and explores the possible influence mechanism,namely,focus on media information.The study is based on internet survey data of 1373 residents in China.A series of econometric models are developed to estimate food safety knowledge and behavior of residents.Both the descriptive and econometric results indicate that the existence of COVID-19 cases in a community has a significantly positive effect on residents’food safety knowledge and behavior.Residents focusing on food safety-related information tend to have higher food safety knowledge and practice food safety behavior.When controlling the variable focused on food safety-related information,the marginal effects of the existence of COVID-19 cases in a community on residents’food safety knowledge and behavior significantly decrease.However,the decrease in consumers’food safety knowledge is quite minor.Hence,the COVID-19 pandemic indeed improves Chinese residents’food safety knowledge and behavior,while focus on food safety-related information is an important mechanism for improving food safety behavior.Moreover,the estimation results of the simultaneous equations model reveal that consumers’food safety knowledge has a significant and positive effect on their food safety behavior.Heterogeneous impacts of the COVID-19 pandemic on residents’food safety knowledge and behavior among different regions and income groups are observed.The findings of this study provide evidence that public health events could enhance residents’safety awareness and behavior,while residents’focus on relevant information plays an important role in improving knowledge and impacting behavior.展开更多
The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphologi...The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight.Notably,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 cells.Furthermore,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific enolase.Additionally,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells.The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment.Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.展开更多
AIM: To evaluate the possible role of Tribble 3 (TRB3) in a rat model of non-alcoholic fatty liver disease (NAFLD) and its signal transduction mechanism.METHODS: Thirty Sprague-Dawley rats were randomized into t...AIM: To evaluate the possible role of Tribble 3 (TRB3) in a rat model of non-alcoholic fatty liver disease (NAFLD) and its signal transduction mechanism.METHODS: Thirty Sprague-Dawley rats were randomized into three groups: normal control group, non-alcoholic fatty liver group A (fed on a high-fat diet for 8 wk) and group B (fed on a high-fat diet for 16 wk). To determine the degree of hepatic steatosis in rats of each group, livers were stained with hematoxylin and eosin, and evaluated; real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRI33 mRNA, and Western blotting analysis was done to determine the expression levels of protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt-Thr308, p-Akt-Ser473).RESULTS: Hepatic steatosis was evident in both NAFLD groups: mild to moderate hepatic steatosis occurred in group A, mainly as mild steatosis.Moderate to severe hepatic steatosis occurred in group B, mainly as severe steatosis. The expression level of TRB3 mRNA in group B was significantly higher than in the control group (122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.002) and group A (122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001). There was no significant difference in the expression levels of Akt (1.03 ± 0.53 vs 1.12 ± 0.77,P = 0.729) and p-Akt-Thr308 (0.82 ± 0.45 vs 0.92 ± 0.38, P = 0.592) between group A and the control group. The expression level of Akt and p-Akt-Thr308 in group B was significantly lower than in group A (Akt 0.41 ± 0.16 vs 1.12 ± 0.77, P = 0.008; p-Akt-Thr308 0.47 ± 0.19 vs 0.82 ± 0.45, P = 0.036) and the control group (Akt 0.41 ± 0.16 vs 1.03 ± 0.53, P = 0.018;p-Akt-Thr308 0.47 ± 0.19 vs 0.92 ± 0.38, P = 0.010).The expression level of p-Akt-Ser473 in group A was significantly higher than in group B (1.48 ± 0.50 vs 0.81± 0.39, P = 0.041) as well as the control group (1.48 ± 0.50 vs 0.45 ± 0.26, P = 0.003).CONCLUSION: TRB3 blocks insulin signaling by inhibiting Akt activation, which contributes to insulin resistance. It may be an important factor in the occurrence and development of NAFLD.展开更多
Water-soluble phenolic acids are major bioactive compounds in the medicinal plant species Salvia miltiorrhiza.Phenolic acid biosynthesis is induced by methyl jasmonate(MeJA)in this important Chinese herb.Here,we inves...Water-soluble phenolic acids are major bioactive compounds in the medicinal plant species Salvia miltiorrhiza.Phenolic acid biosynthesis is induced by methyl jasmonate(MeJA)in this important Chinese herb.Here,we investigated the mechanism underlying this induction by analyzing a transcriptome library of S.miltiorrhiza in response to MeJA.Global transcriptome analysis identified the MeJA-responsive R2R3-MYB transcription factor-encoding gene SmMYB1.Overexpressing SmMYB1 significantly promoted phenolic acid accumulation and upregulated the expression of genes encoding key enzymes in the phenolic acid biosynthesis pathway,including cytochrome P450-dependent monooxygenase(CYP98A14).Dual-luciferase(dual-LUC)assays and/or an electrophoretic mobility shift assays(EMSAs)indicated that SmMYB1 activated the expression of CYP98A14,as well as the expression of genes encoding anthocyanin biosynthesis pathway enzymes,including chalcone isomerase(CHI)and anthocyanidin synthase(ANS).In addition,SmMYB1 was shown to interact with SmMYC2 to additively promote CYP98A14 expression compared to the action of SmMYB1 alone.Taken together,these results demonstrate that SmMYB1 is an activator that improves the accumulation of phenolic acids and anthocyanins in S.miltiorrhiza.These findings lay the foundation for in-depth studies of the molecular mechanism underlying MeJA-mediated phenolic acid biosynthesis and for the metabolic engineering of bioactive ingredients in S.miltiorrhiza.展开更多
基金conducted under the framework of the Sino-German “SURUMER Project” funded by the Bundesministerium für Wissenschaft, Technologie und Forschung (BMBF 01LL0919)+1 种基金supported by the China Postdoctoral Science Foundation (2017M620536)the National Natural Science Foundation of China (71742002, 71673008, and 71761137002)
文摘While migration is widely recognized as a valid option for improving farmers’ income, the welfare effects of migration on left-behind family members are ambiguous. This study examines the impacts of migration on left-behind family members’ food consumption and nutrient intake, particularly in remote rural areas in China. Based on household survey data collected from 611 smallholder rubber farmers in Xishuangbanna Dai Autonomous Prefecture of southwestern China, the empirical results suggest that the migration of family members contributes to improving household net income, whereas it negatively affects left-behind family members’ consumption of grain and pork. Migration also leads to a decrease in left-behind family members’ nutrient intake. Surprisingly, the economic returns of farmers’ migration not only do not foster the transformation of household food consumption from a staple food-dominated dietary structure to one including more meat and dairy products but also reduce left-behind family members’ nutrient intake. This study adds to the literature on the impact of farmers’ migration. The findings have important implications for better understanding the impacts of migration on farmers’ livelihood and human capital development in rural China.
基金Supported by The National Key Project of Scientific and Technical Supporting Programs of China, No. 2006BAI02A14National Natural Science Foundation of China, No. 30770996 and No. 30901776
文摘AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples.RESULTS: IL-8 and CXCR1 proteins were both overexpressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.
基金Supported by The National Key Project of Scientific and Technical Supporting Programs of China, No. 2006BAI02A14National Natural Science Foundation of China, No. 30770996 and No. 81172310
文摘AIM: To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC. METHODS: FAP expression was examined in 134 PDAC specimens by immunohistochemistry, and in four pancreatic cancer cell lines (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also analyzed the association between FAP expression in PDAC cells and the clinicopathology of PDAC patients. RESULTS: The results showed that the FAP was expressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at different levels. Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its88-kDa seprase subunit were identif ied. Higher FAP expression in carcinoma cells was associated with tumor size (P < 0.001), fi brotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical outcome (P = 0.0085). CONCLUSION: FAP is highly expressed in carcinoma cells and f ibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.
基金the Ministry of Science and Technology of China(JY03-A-10,2002AA2Z1003 , 2003CB114303) Science and Technology Committee of Shanghai Municipality(03DJ14016).
文摘We used cDNA microarrays containing ~9,000 unigenes to identify 486 salt responsive expressed sequence tags (ESTs) (representing ~450 unigenes) in shoots of the highly salt-tolerant rice variety, Nona Bokra (Oryza sativa L. Ssp.Indica pv. Nona). Some of the genes identified in this study had previously been associated with salt stress. Howeverthe majority were novel, indicating that there is a great number of genes that are induced by salt exposure. Analysis of the salt stress expression profile data of Nona provided clues regarding some putative cellular and molecular processes that are undertaken by this tolerant rice variety in response to salt stress. Namely, we found that multiple transcription factors were induced during the initial salt response of shoots. Many genes whose encoded proteins are implicated in detoxification, protectant and transport were rapidly induced. Genes supporting photosynthesis were repressed and those supporting carbohydrate metabolism were altered. Commonality among the genes induced by salt exposure with those induced during senescence and biotic stress responses suggests that there are shared signaling pathways among these processes. We further compared the transcriptome changes of the salt-sensitive cultivar, IR28, with that of Nona rice. Many genes that are salt responsive in Nona were found to be differentially regulated in IR28. This study identified a large number of candidate functional genes that appear to be involved in salt tolerance and further examination of these genes may enable the molecular basis of salt tolerance to be elucidated.
基金Supported by Shanghai Municipal Health Bureau Key Disciplines Grant,No.ZK2012A05Bootstrap Class project Foundation of the Science and Technology Commission of Shanghai Municipality,No.14411973700Shanghai Municipal Health Bureau,No.20134100
文摘AIM: To explore the effect of the histone deacetylase inhibitor givinostat on proteins related to regulation of hepatic stellate cell proliferation.METHODS: The cell counting kit-8 assay and flow cytometry were used to observe changes in proliferation, apoptosis, and cell cycle in hepatic stellate cells treated with givinostat. Western blot was used to observe expression changes in p21, p57, CDK4, CDK6, cyclin D1, caspase-3, and caspase-9 in hepatic stellate cells exposed to givinostat. The scratch assay was used to analyze the effect of givinostat on cell migration. Effects of givinostat on the reactive oxygen species profile, mitochondrial membrane potential, and mitochondrial permeability transition pore opening in JS-1 cells were observed by laser confocal microscopy.RESULTS: Givinostat significantly inhibited JS-1 cell proliferation and promoted cell apoptosis, leading to cell cycle arrest in G0/G1 phases. Treatment with givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas expression of p21 and p57 was significantly increased. The givinostat-induced apoptosis of hepatic stellate cells was mainly mediatedthrough p38 and extracellular signal-regulated kinase 1/2. Givinostat treatment increased intracellular reactive oxygen species production, decreased mitochondrial membrane potential, and promoted mitochondrial permeability transition pore opening. Acetylation of superoxide dismutase(acetyl K68) and nuclear factor-κB p65(acetyl K310) was upregulated, while there was no change in protein expression. Moreover, the notable beneficial effect of givinostat on liver fibrosis was also confirmed in the mouse models.CONCLUSION: Givinostat has antifibrotic activities via regulating the acetylation of nuclear factor-κB and superoxide dismutase 2, thus inhibiting hepatic stellate cell proliferation and inducing apoptosis.
基金We acknowledge the funding support from the Huazhong Agricultural University Scientific&Technological Self-innovation Foundation Chinathe Philosophy and Social Sciences Project of Ministry of Education of China(19YJC630191)+1 种基金the Fundamental Research Funds for the Central University,China(2662020JGPYG15)the National Science and Technology Major Project,China(2018ZX08015001).
文摘This study assesses the impacts of the COVID-19 pandemic on Chinese residents’food safety knowledge and behavior,and explores the possible influence mechanism,namely,focus on media information.The study is based on internet survey data of 1373 residents in China.A series of econometric models are developed to estimate food safety knowledge and behavior of residents.Both the descriptive and econometric results indicate that the existence of COVID-19 cases in a community has a significantly positive effect on residents’food safety knowledge and behavior.Residents focusing on food safety-related information tend to have higher food safety knowledge and practice food safety behavior.When controlling the variable focused on food safety-related information,the marginal effects of the existence of COVID-19 cases in a community on residents’food safety knowledge and behavior significantly decrease.However,the decrease in consumers’food safety knowledge is quite minor.Hence,the COVID-19 pandemic indeed improves Chinese residents’food safety knowledge and behavior,while focus on food safety-related information is an important mechanism for improving food safety behavior.Moreover,the estimation results of the simultaneous equations model reveal that consumers’food safety knowledge has a significant and positive effect on their food safety behavior.Heterogeneous impacts of the COVID-19 pandemic on residents’food safety knowledge and behavior among different regions and income groups are observed.The findings of this study provide evidence that public health events could enhance residents’safety awareness and behavior,while residents’focus on relevant information plays an important role in improving knowledge and impacting behavior.
基金supported by the National Natural Science Foundation of China (Grant No. 81700723)Research Project of Jiangsu 333 Engineering (Grant No. BRA2016232)Research Project of Jiangsu Provincial Commission of Health and Family Planning (Grant No. F201549/H201667)
文摘The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight.Notably,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 cells.Furthermore,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific enolase.Additionally,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells.The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment.Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.
文摘AIM: To evaluate the possible role of Tribble 3 (TRB3) in a rat model of non-alcoholic fatty liver disease (NAFLD) and its signal transduction mechanism.METHODS: Thirty Sprague-Dawley rats were randomized into three groups: normal control group, non-alcoholic fatty liver group A (fed on a high-fat diet for 8 wk) and group B (fed on a high-fat diet for 16 wk). To determine the degree of hepatic steatosis in rats of each group, livers were stained with hematoxylin and eosin, and evaluated; real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRI33 mRNA, and Western blotting analysis was done to determine the expression levels of protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt-Thr308, p-Akt-Ser473).RESULTS: Hepatic steatosis was evident in both NAFLD groups: mild to moderate hepatic steatosis occurred in group A, mainly as mild steatosis.Moderate to severe hepatic steatosis occurred in group B, mainly as severe steatosis. The expression level of TRB3 mRNA in group B was significantly higher than in the control group (122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.002) and group A (122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001). There was no significant difference in the expression levels of Akt (1.03 ± 0.53 vs 1.12 ± 0.77,P = 0.729) and p-Akt-Thr308 (0.82 ± 0.45 vs 0.92 ± 0.38, P = 0.592) between group A and the control group. The expression level of Akt and p-Akt-Thr308 in group B was significantly lower than in group A (Akt 0.41 ± 0.16 vs 1.12 ± 0.77, P = 0.008; p-Akt-Thr308 0.47 ± 0.19 vs 0.82 ± 0.45, P = 0.036) and the control group (Akt 0.41 ± 0.16 vs 1.03 ± 0.53, P = 0.018;p-Akt-Thr308 0.47 ± 0.19 vs 0.92 ± 0.38, P = 0.010).The expression level of p-Akt-Ser473 in group A was significantly higher than in group B (1.48 ± 0.50 vs 0.81± 0.39, P = 0.041) as well as the control group (1.48 ± 0.50 vs 0.45 ± 0.26, P = 0.003).CONCLUSION: TRB3 blocks insulin signaling by inhibiting Akt activation, which contributes to insulin resistance. It may be an important factor in the occurrence and development of NAFLD.
基金the National Key R&G Program of China(2018YFC1706200)the National Natural Science Fund(81522049,31571735,31270007)+4 种基金the“Dawn”Program of the Shanghai Education Commission(16SG38)the Shanghai Science and Technology Committee Project(17JC1404300,15430502700)the Zhejiang Provincial Ten Thousands Program for Leading Talents of Science and Technology Innovation(2018R52050)the Zhejiang Natural Science Fund(LY20H280008)the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents,PreResearch Projects of Zhejiang Chinese Medical University(2018ZG30).
文摘Water-soluble phenolic acids are major bioactive compounds in the medicinal plant species Salvia miltiorrhiza.Phenolic acid biosynthesis is induced by methyl jasmonate(MeJA)in this important Chinese herb.Here,we investigated the mechanism underlying this induction by analyzing a transcriptome library of S.miltiorrhiza in response to MeJA.Global transcriptome analysis identified the MeJA-responsive R2R3-MYB transcription factor-encoding gene SmMYB1.Overexpressing SmMYB1 significantly promoted phenolic acid accumulation and upregulated the expression of genes encoding key enzymes in the phenolic acid biosynthesis pathway,including cytochrome P450-dependent monooxygenase(CYP98A14).Dual-luciferase(dual-LUC)assays and/or an electrophoretic mobility shift assays(EMSAs)indicated that SmMYB1 activated the expression of CYP98A14,as well as the expression of genes encoding anthocyanin biosynthesis pathway enzymes,including chalcone isomerase(CHI)and anthocyanidin synthase(ANS).In addition,SmMYB1 was shown to interact with SmMYC2 to additively promote CYP98A14 expression compared to the action of SmMYB1 alone.Taken together,these results demonstrate that SmMYB1 is an activator that improves the accumulation of phenolic acids and anthocyanins in S.miltiorrhiza.These findings lay the foundation for in-depth studies of the molecular mechanism underlying MeJA-mediated phenolic acid biosynthesis and for the metabolic engineering of bioactive ingredients in S.miltiorrhiza.