Introduction:Chemokine-like factor 1(CKLF1)is a chemokine that is overexpressed in several diseases.Our previousfindings revealed a significant increase in CKLF1 expression in the ischemic brain,suggesting its potential...Introduction:Chemokine-like factor 1(CKLF1)is a chemokine that is overexpressed in several diseases.Our previousfindings revealed a significant increase in CKLF1 expression in the ischemic brain,suggesting its potential as a therapeutic target for ischemic stroke.Methods:In this study,we examined the expression dynamics of CKLF1 in both in vivo and in vitro models of ischemic cardiac injury.Myocardial infarction(MI)was induced in vivo by ligation of the left anterior descending artery(LAD)of the rat heart.The levels of CKLF1,Creatine Kinase MB Isoenzyme(CK-MB),and Lactate dehydrogenase(LDH)in the serum were detected using Enzyme-linked immunosorbent assay(ELISA).The expression of CKLF1 in the infarcted area was detected by immunohistochemistry,immunofluorescence,quantitative PCR(qPCR),and Western blotting(WB).H9C2 and AC16 cardiomyocytes cultured in vitro were subjected to oxygen and glucose deprivation(OGD).LDH was used to detect cell damage,and CKLF1 expression was detected by qPCR and WB.Results:CKLF1 mRNA and protein expression were significantly increased in h9c2 cells at 1.5 h and in AC16 cells at 4 h after OGD.The serum CK-MB in rats increased significantly on thefirst day after infarction,while the LDH concentration increased significantly on the third day after infarction.CKLF1 blood levels significantly increased on thefirst day following MI in rats.CKLF1 expression notably increased in the infarct area on days 1,3,and 7 post-MI.In MI tissue,CKLF1 colocalizes with cardiomyocytes,macrophages,and neutrophils.Conclusion:CKLF1 was substantially expressed during myocardial ischemia injury both in vivo and in vitro and was colocalized with macrophages and neutrophils,indicating that CKLF1 is expected to be a biomarker and a drug target for the treatment of myocardial infarction.展开更多
Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischem...Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.展开更多
Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regu...Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.展开更多
Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.展开更多
This study aims to thoroughly investigate the axial power peaking factors (PPF) within the low-enriched uranium (LEU) core of the Ghana Research Reactor-1 (GHARR-1). This study uses advanced simulation tools, like the...This study aims to thoroughly investigate the axial power peaking factors (PPF) within the low-enriched uranium (LEU) core of the Ghana Research Reactor-1 (GHARR-1). This study uses advanced simulation tools, like the MCNPX code for analysing neutron behavior and the PARET/ANL code for understanding power variations, to get a clearer picture of the reactor’s performance. The analysis covers the initial six years of GHARR-1’s operation and includes projections for its whole 60-year lifespan. We closely observed the patterns of both the highest and average PPFs at 21 axial nodes, with measurements taken every ten years. The findings of this study reveal important patterns in power distribution within the core, which are essential for improving the safety regulations and fuel management techniques of the reactor. We provide a meticulous approach, extensive data, and an analysis of the findings, highlighting the significance of continuous monitoring and analysis for proactive management of nuclear reactors. The findings of this study not only enhance our comprehension of nuclear reactor safety but also carry significant ramifications for sustainable energy progress in Ghana and the wider global context. Nuclear engineering is essential in tackling global concerns, such as the demand for clean and dependable energy sources. Research on optimising nuclear reactors, particularly in terms of safety and efficiency, is crucial for the ongoing advancement and acceptance of nuclear energy.展开更多
Introduction: Infant and child mortality is a worldwide concern, but developing countries such as Mali are more affected. The aim of this study was to investigate morbidity and factors associated with mortality in chi...Introduction: Infant and child mortality is a worldwide concern, but developing countries such as Mali are more affected. The aim of this study was to investigate morbidity and factors associated with mortality in children aged 1 month to 15 years. Methodology: This was a cross-sectional study which took place from January 1 to December 31, 2020 covering children aged 1 month to 15 years hospitalized at the Kalaban-Coro CSRéf. Data were entered into Excel and analyzed using SPSS version 20 software. Results: Five hundred children aged 1 months to 15 years were included. The age range 1 to 5 years (53.6%) and male sex (58.2%) were the most represented. Malaria (72.2%), acute respiratory infections (6.2%) and diarrhea/dehydration (3%) were the main morbidities. Mortality was estimated at 10.6%, and the two main causes of death were malaria (56.6%) and acute respiratory infections (7.54%). Univariate analysis revealed a statistically significant association between the dependent variable (death) and age (p Conclusion: This study confirms the high rate of infant and child morbidity and mortality in our health facilities. Strengthening human resources and intensifying behavior-change communication can help reverse the trend.展开更多
基金This work was supported by the National Natural Science Foundation of China(81873026,82074044,81900488,and 81730096)the Beijing Natural Science Foundation(7192135)+1 种基金the Health and Family Planning Commission of Hunan Province(202104010694)the Natural Science Foundation of Hunan Province(2022JJ80028,2023JJ60369).
文摘Introduction:Chemokine-like factor 1(CKLF1)is a chemokine that is overexpressed in several diseases.Our previousfindings revealed a significant increase in CKLF1 expression in the ischemic brain,suggesting its potential as a therapeutic target for ischemic stroke.Methods:In this study,we examined the expression dynamics of CKLF1 in both in vivo and in vitro models of ischemic cardiac injury.Myocardial infarction(MI)was induced in vivo by ligation of the left anterior descending artery(LAD)of the rat heart.The levels of CKLF1,Creatine Kinase MB Isoenzyme(CK-MB),and Lactate dehydrogenase(LDH)in the serum were detected using Enzyme-linked immunosorbent assay(ELISA).The expression of CKLF1 in the infarcted area was detected by immunohistochemistry,immunofluorescence,quantitative PCR(qPCR),and Western blotting(WB).H9C2 and AC16 cardiomyocytes cultured in vitro were subjected to oxygen and glucose deprivation(OGD).LDH was used to detect cell damage,and CKLF1 expression was detected by qPCR and WB.Results:CKLF1 mRNA and protein expression were significantly increased in h9c2 cells at 1.5 h and in AC16 cells at 4 h after OGD.The serum CK-MB in rats increased significantly on thefirst day after infarction,while the LDH concentration increased significantly on the third day after infarction.CKLF1 blood levels significantly increased on thefirst day following MI in rats.CKLF1 expression notably increased in the infarct area on days 1,3,and 7 post-MI.In MI tissue,CKLF1 colocalizes with cardiomyocytes,macrophages,and neutrophils.Conclusion:CKLF1 was substantially expressed during myocardial ischemia injury both in vivo and in vitro and was colocalized with macrophages and neutrophils,indicating that CKLF1 is expected to be a biomarker and a drug target for the treatment of myocardial infarction.
基金Supported by Croatian Ministry of Science and Education,Josip Juraj Strossmayer University of Osijek,Faculty of Dental Medicine and Health,Osijek,Croatia,No.IP7-FDMZ-2023West-Siberian Science and Education Center,Government of Tyumen District,Decree of 20.11.2020,No.928-rpMinistry of Science and Higher Education,No.FMEN 2022-0009.
文摘Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.
基金supported by the Project from the Ministry of Agriculture of China for Transgenic Research(2014ZX0800927B)the National Natural Science Foundation of China(31871667).
文摘Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.
文摘This study aims to thoroughly investigate the axial power peaking factors (PPF) within the low-enriched uranium (LEU) core of the Ghana Research Reactor-1 (GHARR-1). This study uses advanced simulation tools, like the MCNPX code for analysing neutron behavior and the PARET/ANL code for understanding power variations, to get a clearer picture of the reactor’s performance. The analysis covers the initial six years of GHARR-1’s operation and includes projections for its whole 60-year lifespan. We closely observed the patterns of both the highest and average PPFs at 21 axial nodes, with measurements taken every ten years. The findings of this study reveal important patterns in power distribution within the core, which are essential for improving the safety regulations and fuel management techniques of the reactor. We provide a meticulous approach, extensive data, and an analysis of the findings, highlighting the significance of continuous monitoring and analysis for proactive management of nuclear reactors. The findings of this study not only enhance our comprehension of nuclear reactor safety but also carry significant ramifications for sustainable energy progress in Ghana and the wider global context. Nuclear engineering is essential in tackling global concerns, such as the demand for clean and dependable energy sources. Research on optimising nuclear reactors, particularly in terms of safety and efficiency, is crucial for the ongoing advancement and acceptance of nuclear energy.
文摘Introduction: Infant and child mortality is a worldwide concern, but developing countries such as Mali are more affected. The aim of this study was to investigate morbidity and factors associated with mortality in children aged 1 month to 15 years. Methodology: This was a cross-sectional study which took place from January 1 to December 31, 2020 covering children aged 1 month to 15 years hospitalized at the Kalaban-Coro CSRéf. Data were entered into Excel and analyzed using SPSS version 20 software. Results: Five hundred children aged 1 months to 15 years were included. The age range 1 to 5 years (53.6%) and male sex (58.2%) were the most represented. Malaria (72.2%), acute respiratory infections (6.2%) and diarrhea/dehydration (3%) were the main morbidities. Mortality was estimated at 10.6%, and the two main causes of death were malaria (56.6%) and acute respiratory infections (7.54%). Univariate analysis revealed a statistically significant association between the dependent variable (death) and age (p Conclusion: This study confirms the high rate of infant and child morbidity and mortality in our health facilities. Strengthening human resources and intensifying behavior-change communication can help reverse the trend.
