We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cell...AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.展开更多
OVATE family proteins(OFPs)are plant-specific proteins with a conserved OVATE domain that regulate plant growth and development.Although OFPs have been studied in several species,their biological functions remain larg...OVATE family proteins(OFPs)are plant-specific proteins with a conserved OVATE domain that regulate plant growth and development.Although OFPs have been studied in several species,their biological functions remain largely unknown in cucumber(Cucumis sativus L.).This study identified 19 Cs OFPs distributed on seven chromosomes in cucumber.Most Cs OFP genes were expressed in reproductive organs,but with different expression patterns.Ectopic expression of Cs OFP12-16c in Arabidopsis resulted in shorter and blunt siliques.The overall results indicated that Cs OFP12-16c regulates silique development in Arabidopsis and may have a similar function in cucumber.展开更多
Objectives To study the effects of XUEZHIKANG on lipid modulating and the level of oxidized low density lipoprotein(OX - LDL), C -reactive protein(CRP), fibrinogen(FIB) in serum. Methods XUEZHIKANG was given to patien...Objectives To study the effects of XUEZHIKANG on lipid modulating and the level of oxidized low density lipoprotein(OX - LDL), C -reactive protein(CRP), fibrinogen(FIB) in serum. Methods XUEZHIKANG was given to patients with unstable angina pectoris and hyperlipidemia at a dose of 0. 6 gram bid for 2 months and with half -dose for another 2 months. Vitamin E was given to unstable angina pectoris patients with normal lipid at the dose of 0. 1 gram bid for 4 months respectively. Then compared the level of lipid and OX - LDfL, CRP, FIB in serum at beginning, first - month and second -month. Results XUEZHIKANG can reduce the serum level of total cholesterol, low density lipoprotein in 1 month , and gained better effect in 2 months. It can also reduce triglyceride and increase high density lipoprotein in 2 months. Compared with vitamin E XUEZHIKANG can reduce the level of OX - LDL, CRP, FIB significantly after treatment for 2 months. Conclusions XUEZHIKANG has significant effect in lipid modulating , and it can also inhibit the development of inflammation in coronary plaque.展开更多
Objective: To investigate the correlation of serum calcitonin (PCT), interleukin -6 (IL-6), C reactive protein (CRP) and pulmonary ventilation function in patients with acute exacerbation of chronic obstructive pulmon...Objective: To investigate the correlation of serum calcitonin (PCT), interleukin -6 (IL-6), C reactive protein (CRP) and pulmonary ventilation function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: 70 patients with AECOPD in our hospital from May 2017 to May 2018 were selected to be included in the case group, and 70 healthy persons in the same period were selected as the control group. The serum levels of PCT, IL-6, CRP and lung function were compared between the two groups, and the relationship between the serum levels of PCT, IL-6 and CRP and the pulmonary ventilation function of the patients was analyzed. Results: the levels of PCT, IL-6 and CRP in the case group were significantly higher than those in the control group. The difference was statistically significant (P < 0.05), and the FEV1, FEV1/FVC and FEV1% in the case group were significantly lower than those in the control group (P < 0.05), and the difference of PCT, IL-6 and CRP was significant between the patients with different pulmonary function levels, and the statistics were statistically significant. The study significance (P < 0.05), and the level of PCT, IL-6 and CRP increased gradually with the increase of lung function grade, and the level of PCT, IL-6 and CRP in AECOPD patients were negatively correlated with FEV1, FEV1/FVC and FEV1%, and the difference was statistically significant (P < 0.05). Conclusion: the serum levels of PCT, IL-6 and CRP in patients with AECOPD are abnormal increased and are closely related to the pulmonary ventilation function of the patients, which can be used as an important indicator of the monitoring of the patient's condition in AECOPD.展开更多
The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding pla...The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding plays a role in ALS pathogenesis in two ways: non-ATG translation of the repeat can lead to aggregates of the known C9orf72 specific dipeptide polymer, whereas the repeat also can form neurotoxic RNA inclusions that dose-responsively kill motor neurons. We report the presence of a homology in the 5’untranslated region (UTR) of the messenger RNA encoding C9orf72 with the iron responsive elements (IRE) that control expression of iron-associated transcripts and predict that this RNA structure may iron-dependently regulate C9orf72 translation. We previously report altered serum ferritin levels track with severity of ALS in patients. Here, we conduct bioinformatics analyses to determine the secondary structure of the 5’UTR in C9orf72 mRNA and find it aligned with IREs in the human mitochondrial cis-aconitase and L and H-ferritin transcripts. Comparison of the role of RNA repeats in Friedriech’s ataxia and fragile X mental retardation suggests the utility of RNA based therapies for treatment of ALS. Antisense oligonucleotides (ASO) have been reported to therapeutically target these GGGGCC repeats. At the same time, because the function of C9orf72 is unknown, knockdown strategies carry some risk of inducing or compounding haploinsufficiency. We propose, for consideration, an approach that may enhance its therapeutic dynamic range by increasing the 5’UTR driven translation of C9orf72 protein to compensate for any potential ALS-specific or ASO-induced haploinsufficieny.展开更多
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
基金Supported by Medical Specialty Development Projects of Beijing Municipal Administration of Hospitals,No.ZYLX201402Ministry of Education of The People’s Republic of China,No.20121107110012+1 种基金Beijing Municipal Commission of Education,No.11320016Collaborative Innovation Center of Infectious Diseases and Beijing Key Laboratory of Emerging Infectious Diseases,Beijing,China
文摘AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.
基金supported by the National Natural Science Foundation of China(31772315 and 31572132)the Construction of Beijing Science and Technology Innovation and Service Capacity in Top Subjects,China(CEFF-PXM2019_014207_000032)。
文摘OVATE family proteins(OFPs)are plant-specific proteins with a conserved OVATE domain that regulate plant growth and development.Although OFPs have been studied in several species,their biological functions remain largely unknown in cucumber(Cucumis sativus L.).This study identified 19 Cs OFPs distributed on seven chromosomes in cucumber.Most Cs OFP genes were expressed in reproductive organs,but with different expression patterns.Ectopic expression of Cs OFP12-16c in Arabidopsis resulted in shorter and blunt siliques.The overall results indicated that Cs OFP12-16c regulates silique development in Arabidopsis and may have a similar function in cucumber.
文摘Objectives To study the effects of XUEZHIKANG on lipid modulating and the level of oxidized low density lipoprotein(OX - LDL), C -reactive protein(CRP), fibrinogen(FIB) in serum. Methods XUEZHIKANG was given to patients with unstable angina pectoris and hyperlipidemia at a dose of 0. 6 gram bid for 2 months and with half -dose for another 2 months. Vitamin E was given to unstable angina pectoris patients with normal lipid at the dose of 0. 1 gram bid for 4 months respectively. Then compared the level of lipid and OX - LDfL, CRP, FIB in serum at beginning, first - month and second -month. Results XUEZHIKANG can reduce the serum level of total cholesterol, low density lipoprotein in 1 month , and gained better effect in 2 months. It can also reduce triglyceride and increase high density lipoprotein in 2 months. Compared with vitamin E XUEZHIKANG can reduce the level of OX - LDL, CRP, FIB significantly after treatment for 2 months. Conclusions XUEZHIKANG has significant effect in lipid modulating , and it can also inhibit the development of inflammation in coronary plaque.
文摘Objective: To investigate the correlation of serum calcitonin (PCT), interleukin -6 (IL-6), C reactive protein (CRP) and pulmonary ventilation function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: 70 patients with AECOPD in our hospital from May 2017 to May 2018 were selected to be included in the case group, and 70 healthy persons in the same period were selected as the control group. The serum levels of PCT, IL-6, CRP and lung function were compared between the two groups, and the relationship between the serum levels of PCT, IL-6 and CRP and the pulmonary ventilation function of the patients was analyzed. Results: the levels of PCT, IL-6 and CRP in the case group were significantly higher than those in the control group. The difference was statistically significant (P < 0.05), and the FEV1, FEV1/FVC and FEV1% in the case group were significantly lower than those in the control group (P < 0.05), and the difference of PCT, IL-6 and CRP was significant between the patients with different pulmonary function levels, and the statistics were statistically significant. The study significance (P < 0.05), and the level of PCT, IL-6 and CRP increased gradually with the increase of lung function grade, and the level of PCT, IL-6 and CRP in AECOPD patients were negatively correlated with FEV1, FEV1/FVC and FEV1%, and the difference was statistically significant (P < 0.05). Conclusion: the serum levels of PCT, IL-6 and CRP in patients with AECOPD are abnormal increased and are closely related to the pulmonary ventilation function of the patients, which can be used as an important indicator of the monitoring of the patient's condition in AECOPD.
文摘The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding plays a role in ALS pathogenesis in two ways: non-ATG translation of the repeat can lead to aggregates of the known C9orf72 specific dipeptide polymer, whereas the repeat also can form neurotoxic RNA inclusions that dose-responsively kill motor neurons. We report the presence of a homology in the 5’untranslated region (UTR) of the messenger RNA encoding C9orf72 with the iron responsive elements (IRE) that control expression of iron-associated transcripts and predict that this RNA structure may iron-dependently regulate C9orf72 translation. We previously report altered serum ferritin levels track with severity of ALS in patients. Here, we conduct bioinformatics analyses to determine the secondary structure of the 5’UTR in C9orf72 mRNA and find it aligned with IREs in the human mitochondrial cis-aconitase and L and H-ferritin transcripts. Comparison of the role of RNA repeats in Friedriech’s ataxia and fragile X mental retardation suggests the utility of RNA based therapies for treatment of ALS. Antisense oligonucleotides (ASO) have been reported to therapeutically target these GGGGCC repeats. At the same time, because the function of C9orf72 is unknown, knockdown strategies carry some risk of inducing or compounding haploinsufficiency. We propose, for consideration, an approach that may enhance its therapeutic dynamic range by increasing the 5’UTR driven translation of C9orf72 protein to compensate for any potential ALS-specific or ASO-induced haploinsufficieny.
