Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor c...Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.展开更多
Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulo...Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.展开更多
Background:Intervertebral disc degeneration(IVDD)is a multifaceted condition characterized by heterogeneity,wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus(NP)cells...Background:Intervertebral disc degeneration(IVDD)is a multifaceted condition characterized by heterogeneity,wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus(NP)cells plays a central role.Presently,the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes.D-mannose(referred to as mannose)has demonstrated anti-catabolic properties in various diseases.Nevertheless,its therapeutic potential in IVDD has yet to be explored.Methods:The study began with optimizing the mannose concentration for restoring NP cells.Transcriptomic analyses were employed to identify the mediators influenced by mannose,with the thioredoxin-interacting protein(TXNIP)gene showing the most significant differences.Subsequently,small interfering RNA(siRNA)technology was used to demonstrate that TXNIP is the key gene through which mannose exerts its effects.Techniques such as colocalization analysis,molecular docking,and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP.To elucidate the mechanism of action of mannose,metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose.Next,various methods,including integrated omics data and the Gene Expression Omnibus(GEO)database,were used to validate the one-way pathway through which TXNIP regulates glutamine.Finally,the therapeutic effect of mannose on IVDD was validated,elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.Results:In both in vivo and in vitro experiments,it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism.From a mechanistic standpoint,it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein(MondoA),resulting in the upregulation of TXNIP.This upregulation,in turn,inhibits glutamine metabolism,ultimately accomplishing its anticatabolic effects by suppressing the mitogen-activated protein kinase(MAPK)pathway.More importantly,in vivo experiments have further demonstrated that compared with intradiscal injections,oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes.Conclusions:In summary,through integrated multiomics analysis,including both in vivo and in vitro experiments,this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis.These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD.Compared to existing clinically invasive or pain-relieving therapies for IVDD,the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.展开更多
基金supported by the National Natural Science Foundation of China,No.30772229(to JNZ),No.81200907(to HJW)the Natural Science Foundation of Tianjin of China,No.12JCQNJC06800(to HJW)+1 种基金the Science and Technology Projects in Key Areas of Traditional Chinese Medicine of Tianjin of China,No.2018001(to ZGW)the Scientific Research Program Project of Tianjin Education Commission of China,No.2018ZD03(to ZGW)
文摘Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.
基金supported by the National Natural Science Foundation of China,No.81330029(to JNZ),81501057(to YT)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education in China,No.2016YD02(to YW)the Technology Program Fund of Tianjin Health and Family Planning Commission for the Key Field of Traditional Chinese Medicine,No.2018001(to ZGW)
文摘Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.
基金supported by the National Key Research and Development Program of China(2020YFB1711505).
文摘Background:Intervertebral disc degeneration(IVDD)is a multifaceted condition characterized by heterogeneity,wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus(NP)cells plays a central role.Presently,the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes.D-mannose(referred to as mannose)has demonstrated anti-catabolic properties in various diseases.Nevertheless,its therapeutic potential in IVDD has yet to be explored.Methods:The study began with optimizing the mannose concentration for restoring NP cells.Transcriptomic analyses were employed to identify the mediators influenced by mannose,with the thioredoxin-interacting protein(TXNIP)gene showing the most significant differences.Subsequently,small interfering RNA(siRNA)technology was used to demonstrate that TXNIP is the key gene through which mannose exerts its effects.Techniques such as colocalization analysis,molecular docking,and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP.To elucidate the mechanism of action of mannose,metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose.Next,various methods,including integrated omics data and the Gene Expression Omnibus(GEO)database,were used to validate the one-way pathway through which TXNIP regulates glutamine.Finally,the therapeutic effect of mannose on IVDD was validated,elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.Results:In both in vivo and in vitro experiments,it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism.From a mechanistic standpoint,it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein(MondoA),resulting in the upregulation of TXNIP.This upregulation,in turn,inhibits glutamine metabolism,ultimately accomplishing its anticatabolic effects by suppressing the mitogen-activated protein kinase(MAPK)pathway.More importantly,in vivo experiments have further demonstrated that compared with intradiscal injections,oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes.Conclusions:In summary,through integrated multiomics analysis,including both in vivo and in vitro experiments,this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis.These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD.Compared to existing clinically invasive or pain-relieving therapies for IVDD,the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.
