Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we i...Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.展开更多
To study the effect of Green plum citron double strain fermentation filtrate(DSF)on the proliferation rate of HaCaT keratinocytes by CCK8 assay.The effect of DSF on the mRNA transcription levels of filagolin(FLG),lori...To study the effect of Green plum citron double strain fermentation filtrate(DSF)on the proliferation rate of HaCaT keratinocytes by CCK8 assay.The effect of DSF on the mRNA transcription levels of filagolin(FLG),loricrin(LOR),and occludin 1(CLD1)in HaCaT cells in sodium dodecyl sulfate(SLS)model was investigated by qPCR.The effect of DSF on the content of TNF-αin the supernatant of HaCaT cells in the model was investigated by Elisa.The results showed that DSF had no toxicity to HaCaT cells,but it could increase the mRNA transcription levels of FLG,LOR and CLD1 in HaCaT cells in the model,and reduce the content of TNF-αin the supernatant of HaCaT cells in the model.DSF had a certain effect on skin care of strengthening skin barrier.展开更多
Objective:To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma (HCC).Methods:Patients with unresectable advanced HCC received cryoabla...Objective:To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma (HCC).Methods:Patients with unresectable advanced HCC received cryoablation and sorafenib at a dose of 400 mg twice daily in 4-week cycles on the same day of the cryoablation.Tumor response,median overall survival and the median time to radiological progression were calculated and the toxicity was evaluated.Results:Seventy-eight patients with unresectable HCC were involved in this study.The median age was 52 years (range,22-81 years).The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0 (39.7%),1 (55.1%),and 2 (5.1%).Nine (11.5%) patients were at Barcelona clinic liver cancer (BCLC) stage A,twenty-four (30.8%) patients were at stage B and 45 (57.7%) patients were at stage C.Five (6.4%) achieved partial responses,and 34 (43.6%) achieved stable disease.The median time to progression (TTP) for all enrolled patients was 6.6 months and the median overall survival (OS) was 12.2 months.Conclusion:Cryoablation combined with sorafenib demonstrates good efficacy and acceptable tolerability in treating unresectable advanced HCC patients.展开更多
BACKGROUND: Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2+. Zn^2+ metabolism in the mossy fiber pathway, and Zn^2+ accumulation in presy...BACKGROUND: Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2+. Zn^2+ metabolism in the mossy fiber pathway, and Zn^2+ accumulation in presynaptic membrane vesicles, are dependent on zinc transporter 1 (ZnT1) and glutamate receptor subunit 2 (GluR2). OBJECTIVE: To investigate the effects of long-term recurrent neonatal seizure, in the presence and absence of physical exercise, on the developmental expression of hippocampal zinc transporter 1 (ZnT1) and GluR2, and on cognitive function in rats. DESIGN, TIME AND SETTING: Based on behavioral examination and molecular biological research, a randomized, controlled animal experiment was performed at the Department of Neurobiology, Medical College of Soochow University, between January 2007 and April 2008. MATERIALS: Twenty-one 6-day-old Sprague Dawley rats of either gender were employed in this study. ZnT1 mRNA in situ hybridization kit was provided by Tianjin Haoyang Biological Manufacture Co.,Ltd., China. Rabbit anti-GluR2 was purchased from Santa Cruz Biotech, Inc, USA. METHODS: Rats were randomly divided into a recurrent seizure group (n = 11) and a control group (n = 10). In the recurrent seizure group, 30-minute seizure was induced by flurothyl gas inhalation for a total of 6 consecutive days. Rats from the control group underwent experimental procedures similar to the recurrent seizure group, with the exception of flurothyl gas inhalation. Thirty minutes of treadmill exercise was performed daily by all rats at postnatal days 51–56. MAIN OUTCOME MEASURES: At postnatal day 82, rat hippocampal tissue was harvested for analysis of hippocampal ZnT1 and GluR2 expression by in situ hybridization and immunohistochemistry, respectively. Rat learning and memory capabilities were examined using the Y-maze test. RESULTS: In the recurrent seizure group, the gray scale value of ZnT1 in situ hybridization positive neurons in the hippocampal CA3 region was significantly greater (P 〈 0.05), while the gray scale value of GluR2 immunoreactive neurons in the hippocampal hilus and dentate gyrus was significantly lower (P 〈 0.05), than in the control group. At postnatal days 29–35, numbers of trials to criteria for successful learning were greater in the recurrent seizure group than in the control group (P 〈 0.05); at postnatal days 61–67, the numbers of trials to criteria for successful learning were similar between the two groups (P 〉 0.05). At postnatal days 29–35 and 61–67, there was no significant difference in memory capability between the recurrent seizure and control groups (P 〉 0.05). CONCLUSION: Physical exercise likely improves the learning deficits caused by recurrent neonatal seizure in rats during brain development by modulating ZnT1 and GluR2 expression.展开更多
BACKGROUND: Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2+ metabolism has been sh...BACKGROUND: Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2+ metabolism has been shown to contribute to the regenerative sprouting of hippocampal mossy fibers Furthermore, zinc transporter-3 (ZnT3) is responsible for Zn^2+ transport in the hippocampal mossy fiber pathway. OBJECTIVE: To investigate the effects of long-term recurrent neonatal seizures on learning, memory formation and hippocampal ZnT3 expression in rats. DESIGN, TIME AND SETTING: Based on molecular biological research and behavioral examination a randomized, controlled, animal experiment was performed at the Laboratory Animal Center, Peking University Health Science Center, between October 2004 and July 2005. MATERIALS: Flurothyl was purchased from Aldrich Chemical Co., USA. ZnT3 mRNA in situ hybridization kits were provided by Tianjin Haoyang Biological Manufacture Co., Ltd., China. Morris water maze was produced by Shanghai Jiliang Science and Technology Co., Ltd., China. METHODS: Sixty, 6-day old, Wistar rats were randomly divided into three groups: single seizure (n = 21), recurrent seizure (n = 21, one seizure daily for 6 consecutive days), and control (n = 18). Seizures were induced by flurothyl gas inhalation, in the single seizure and recurrent seizure groups. MAIN OUTCOME MEASURES: At postnatal days 12, 46 and 90, rat hippocampal ZnT3 mRNA expression was detected by RT-PCR; at postnatal days 46 and 90, ZnT3 mRNA expression was determined by in situ hybridization; and at postnatal days 41-46 and 85 90, rat spatial learning and memory formation were examined by the Morris water maze test. RESULTS: RT-PCR results revealed that at postnatal day 12, ZnT3 expression was significantly greater in the recurrent seizure group than in the control and single seizure groups, and at day 46, it was also significantly greater in the recurrent seizure group compared with the control group (P 〈 0.05). In situ hybridization results showed that at postnatal day 46, the recurrent seizure group exhibited increased hippocampal ZnT3 expression over the control and single seizure groups (P〈0.05). Morris water maze test results displayed that, in the first place navigation test at postnatal day 44, and the second test at days 87-88, the recurrent seizure group exhibited significantly higher value of average escape latency compared with the control group (P 〈 0.05). In the two spatial probe tests, the search strategies were significantly inferior in the recurrent seizure group than in the control and single seizure groups (P 〈 0.05). CONCLUSION: Neonatal concurrent seizures produce long-term damaging effects on hippocampal ZnT3 expression and cognitive function, while both of which have no parallel correlation.展开更多
Electroplating waste water is considered to be harmful to health of animals. In the present study, we tested the hypothesis that electroplating waste water would suppress immune functions in Kunming mice. Twenty-six m...Electroplating waste water is considered to be harmful to health of animals. In the present study, we tested the hypothesis that electroplating waste water would suppress immune functions in Kunming mice. Twenty-six mice were randomly divided into the control group (n = 13) and the experimental group (n = 13), in which the latter drank electroplating waste water. We found that body mass and most organ wet masses (heart, lungs, liver, kidneys, stomach, caecum, colon, testes, epididymis, seminal vesicals) were not influenced by electroplating waste water. However, stomach with its content, small intestine, small intestine with its contents and colon with its contents were higher in the experimental group than in the control group. As expected, phytohaemagglutinin (PHA) response indicative of cellular immunity was suppressed by electroplating waste water. White blood cells, thymus and spleen mass were all not response to electroplating waste water. Taken together, electroplating waste water had different effects on distinct components of immune system in Kunming mice.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81871024 (to HN),82301957 (to XW),82001382 (to LL),62127810 (to HN)the Natural Science Foundation of Jiangsu Province of China,No.SBK2020040785 (to LL)。
文摘Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.
文摘To study the effect of Green plum citron double strain fermentation filtrate(DSF)on the proliferation rate of HaCaT keratinocytes by CCK8 assay.The effect of DSF on the mRNA transcription levels of filagolin(FLG),loricrin(LOR),and occludin 1(CLD1)in HaCaT cells in sodium dodecyl sulfate(SLS)model was investigated by qPCR.The effect of DSF on the content of TNF-αin the supernatant of HaCaT cells in the model was investigated by Elisa.The results showed that DSF had no toxicity to HaCaT cells,but it could increase the mRNA transcription levels of FLG,LOR and CLD1 in HaCaT cells in the model,and reduce the content of TNF-αin the supernatant of HaCaT cells in the model.DSF had a certain effect on skin care of strengthening skin barrier.
文摘Objective:To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma (HCC).Methods:Patients with unresectable advanced HCC received cryoablation and sorafenib at a dose of 400 mg twice daily in 4-week cycles on the same day of the cryoablation.Tumor response,median overall survival and the median time to radiological progression were calculated and the toxicity was evaluated.Results:Seventy-eight patients with unresectable HCC were involved in this study.The median age was 52 years (range,22-81 years).The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0 (39.7%),1 (55.1%),and 2 (5.1%).Nine (11.5%) patients were at Barcelona clinic liver cancer (BCLC) stage A,twenty-four (30.8%) patients were at stage B and 45 (57.7%) patients were at stage C.Five (6.4%) achieved partial responses,and 34 (43.6%) achieved stable disease.The median time to progression (TTP) for all enrolled patients was 6.6 months and the median overall survival (OS) was 12.2 months.Conclusion:Cryoablation combined with sorafenib demonstrates good efficacy and acceptable tolerability in treating unresectable advanced HCC patients.
基金the National Natural Science Foundation of China, No. 30470555, 30571909, 30870808the Natural Science Foundation of Jiangsu Province, No. BK2007509Natural Science Foundation for Colleges and Universities in Jiangsu Province, No. 07KJB320103
文摘BACKGROUND: Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2+. Zn^2+ metabolism in the mossy fiber pathway, and Zn^2+ accumulation in presynaptic membrane vesicles, are dependent on zinc transporter 1 (ZnT1) and glutamate receptor subunit 2 (GluR2). OBJECTIVE: To investigate the effects of long-term recurrent neonatal seizure, in the presence and absence of physical exercise, on the developmental expression of hippocampal zinc transporter 1 (ZnT1) and GluR2, and on cognitive function in rats. DESIGN, TIME AND SETTING: Based on behavioral examination and molecular biological research, a randomized, controlled animal experiment was performed at the Department of Neurobiology, Medical College of Soochow University, between January 2007 and April 2008. MATERIALS: Twenty-one 6-day-old Sprague Dawley rats of either gender were employed in this study. ZnT1 mRNA in situ hybridization kit was provided by Tianjin Haoyang Biological Manufacture Co.,Ltd., China. Rabbit anti-GluR2 was purchased from Santa Cruz Biotech, Inc, USA. METHODS: Rats were randomly divided into a recurrent seizure group (n = 11) and a control group (n = 10). In the recurrent seizure group, 30-minute seizure was induced by flurothyl gas inhalation for a total of 6 consecutive days. Rats from the control group underwent experimental procedures similar to the recurrent seizure group, with the exception of flurothyl gas inhalation. Thirty minutes of treadmill exercise was performed daily by all rats at postnatal days 51–56. MAIN OUTCOME MEASURES: At postnatal day 82, rat hippocampal tissue was harvested for analysis of hippocampal ZnT1 and GluR2 expression by in situ hybridization and immunohistochemistry, respectively. Rat learning and memory capabilities were examined using the Y-maze test. RESULTS: In the recurrent seizure group, the gray scale value of ZnT1 in situ hybridization positive neurons in the hippocampal CA3 region was significantly greater (P 〈 0.05), while the gray scale value of GluR2 immunoreactive neurons in the hippocampal hilus and dentate gyrus was significantly lower (P 〈 0.05), than in the control group. At postnatal days 29–35, numbers of trials to criteria for successful learning were greater in the recurrent seizure group than in the control group (P 〈 0.05); at postnatal days 61–67, the numbers of trials to criteria for successful learning were similar between the two groups (P 〉 0.05). At postnatal days 29–35 and 61–67, there was no significant difference in memory capability between the recurrent seizure and control groups (P 〉 0.05). CONCLUSION: Physical exercise likely improves the learning deficits caused by recurrent neonatal seizure in rats during brain development by modulating ZnT1 and GluR2 expression.
基金the National Natural Science Foundation of China,No.30470555, 30870808the Natural Science Foundation of Jiangsu Province of China, No.BK2007509the Natural Science Foundation for Higher Education Institutions in Jiangsu Province, No.07KJB320103
文摘BACKGROUND: Developmental seizures, which are pathologically characterized by regenerative sprouting of hippocampal mossy fibers, cause long-term damaging effects to synaptic plasticity. Zn^2+ metabolism has been shown to contribute to the regenerative sprouting of hippocampal mossy fibers Furthermore, zinc transporter-3 (ZnT3) is responsible for Zn^2+ transport in the hippocampal mossy fiber pathway. OBJECTIVE: To investigate the effects of long-term recurrent neonatal seizures on learning, memory formation and hippocampal ZnT3 expression in rats. DESIGN, TIME AND SETTING: Based on molecular biological research and behavioral examination a randomized, controlled, animal experiment was performed at the Laboratory Animal Center, Peking University Health Science Center, between October 2004 and July 2005. MATERIALS: Flurothyl was purchased from Aldrich Chemical Co., USA. ZnT3 mRNA in situ hybridization kits were provided by Tianjin Haoyang Biological Manufacture Co., Ltd., China. Morris water maze was produced by Shanghai Jiliang Science and Technology Co., Ltd., China. METHODS: Sixty, 6-day old, Wistar rats were randomly divided into three groups: single seizure (n = 21), recurrent seizure (n = 21, one seizure daily for 6 consecutive days), and control (n = 18). Seizures were induced by flurothyl gas inhalation, in the single seizure and recurrent seizure groups. MAIN OUTCOME MEASURES: At postnatal days 12, 46 and 90, rat hippocampal ZnT3 mRNA expression was detected by RT-PCR; at postnatal days 46 and 90, ZnT3 mRNA expression was determined by in situ hybridization; and at postnatal days 41-46 and 85 90, rat spatial learning and memory formation were examined by the Morris water maze test. RESULTS: RT-PCR results revealed that at postnatal day 12, ZnT3 expression was significantly greater in the recurrent seizure group than in the control and single seizure groups, and at day 46, it was also significantly greater in the recurrent seizure group compared with the control group (P 〈 0.05). In situ hybridization results showed that at postnatal day 46, the recurrent seizure group exhibited increased hippocampal ZnT3 expression over the control and single seizure groups (P〈0.05). Morris water maze test results displayed that, in the first place navigation test at postnatal day 44, and the second test at days 87-88, the recurrent seizure group exhibited significantly higher value of average escape latency compared with the control group (P 〈 0.05). In the two spatial probe tests, the search strategies were significantly inferior in the recurrent seizure group than in the control and single seizure groups (P 〈 0.05). CONCLUSION: Neonatal concurrent seizures produce long-term damaging effects on hippocampal ZnT3 expression and cognitive function, while both of which have no parallel correlation.
文摘Electroplating waste water is considered to be harmful to health of animals. In the present study, we tested the hypothesis that electroplating waste water would suppress immune functions in Kunming mice. Twenty-six mice were randomly divided into the control group (n = 13) and the experimental group (n = 13), in which the latter drank electroplating waste water. We found that body mass and most organ wet masses (heart, lungs, liver, kidneys, stomach, caecum, colon, testes, epididymis, seminal vesicals) were not influenced by electroplating waste water. However, stomach with its content, small intestine, small intestine with its contents and colon with its contents were higher in the experimental group than in the control group. As expected, phytohaemagglutinin (PHA) response indicative of cellular immunity was suppressed by electroplating waste water. White blood cells, thymus and spleen mass were all not response to electroplating waste water. Taken together, electroplating waste water had different effects on distinct components of immune system in Kunming mice.