BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of c...BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of cases.HCC is the most common primary liver cancer.China has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese people.The onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when diagnosed.Therefore,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of patients.Protein tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further studied.AIM To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in HCC.METHODS The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and immunoblotting.The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features.Finally,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.RESULTS The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways,including cancer-related pathways,the Notch signaling pathway,and the MAPK signaling pathway.Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways,such as the epithelial mesenchymal transition process.A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.CONCLUSION This study investigated PTPN2 from multiple biological perspectives,revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.展开更多
Bacteria play critical roles in regulating soil phosphorus(P) cycling. The effects of interactions between crops and soil P-availability on bacterial communities and the feedback regulation of soil P cycling by the ba...Bacteria play critical roles in regulating soil phosphorus(P) cycling. The effects of interactions between crops and soil P-availability on bacterial communities and the feedback regulation of soil P cycling by the bacterial community modifications are poorly understood. Here, six soybean(Glycine max) genotypes with differences in P efficiency were cultivated in acidic soils with long-term sufficient or deficient P-fertilizer treatments. The acid phosphatase(AcP) activities, organic-P concentrations and associated bacterial community compositions were determined in bulk and rhizosphere soils. The results showed that both soybean plant P content and the soil AcP activity were negatively correlated with soil organic-P concentration in P-deficient acidic soils. Soil P-availability affected the ɑ-diversity of bacteria in both bulk and rhizosphere soils. However, soybean had a stronger effect on the bacterial community composition, as reflected by the similar biomarker bacteria in the rhizosphere soils in both P-treatments. The relative abundance of biomarker bacteria Proteobacteria was strongly correlated with soil organic-P concentration and AcP activity in low-P treatments. Further high-throughput sequencing of the phoC gene revealed an obvious shift in Proteobacteria groups between bulk soils and rhizosphere soils, which was emphasized by the higher relative abundances of Cupriavidus and Klebsiella, and lower relative abundance of Xanthomonas in rhizosphere soils. Among them, Cupriavidus was the dominant phoC bacterial genus, and it was negatively correlated with the soil organic-P concentration. These findings suggest that soybean growth relies on organic-P mineralization in P-deficient acidic soils, which might be partially achieved by recruiting specific phoCharboring bacteria, such as Cupriavidus.展开更多
BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high ...BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high incidence worldwide.As a common local treatment,RFA has attracted much attention for its efficacy and influence on liver function.AIM To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA.METHODS The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected.The chi-square test was used to compare the data between groups.The Kaplan-Meier method and Cox regression were used to analyze the associ-ations between serum ALP and GGT levels and overall survival,progression-free survival(PFS)and clinical characteristics of patients before treatment.RESULTS The 1-year survival rates of patients with normal(≤135 U/L)and abnormal(>135 U/L)serum ALP before treatment were 91%and 79%,respectively;the 2-year survival rates were 90%and 68%,respectively;and the 5-year survival rates were 35%and 18%,respectively.The difference between the two groups was statistically significant(P=0.01).Before treatment,the 1-year survival rates of patients with normal serum GGT levels(≤45 U/L)and abnormal serum GGT levels(>45 U/L)were 95%and 87%,the 2-year survival rates were 85%and 71%,and the 5-year survival rates were 37%and 21%,respectively.The difference between the two groups was statist-ically significant(P<0.001).Serum ALP[hazard ratio(HR)=1.766,95%confidence interval(95%CI):1.068-2.921,P=0.027]and GGT(HR=2.312,95%CI:1.367-3.912,P=0.002)is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor.The 1-year PFS rates were 72%and 50%,the 2-year PFS rates were 52%and 21%,and the 5-year PFS rates were 14%and 3%,respectively.The difference between the two groups was statistically significant(P<0001).The 1-year PFS rates were 81%and 56%in patients with normal and abnormal serum GGT levels before treatment,respectively;the 2-year PFS rates were 62%and 35%,respectively;and the 5-year PFS rates were 18%and 7%,respectively,with statistical significance between the two groups(P<0.001).The serum ALP concentration(HR=1.653,95%CI:1.001-2.729,P=0.049)and GGT(HR=1.949,95%CI:1.296-2.930,P=0.001)was closely associated with PFS after RFA in patients with PLC.The proportion of male patients with abnormal ALP levels is high,the Child-Pugh grade of liver function is poor,and the incidence of ascites is high.Among GGT-abnormal patients,the Child-Pugh grade of liver function was poor,the tumor stage was late,the proportion of patients with tumors≥5 cm was high,and the incidence of hepatic encephalopathy was high.CONCLUSION Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA,and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.展开更多
Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB le...Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.展开更多
Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in trau...Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.展开更多
Background:The diversity of resource acquisition strategies of plant roots determines the species coexistence patterns to a certain extent.However,few root physiological traits have been investigated,such as root phos...Background:The diversity of resource acquisition strategies of plant roots determines the species coexistence patterns to a certain extent.However,few root physiological traits have been investigated,such as root phosphatase activity(PA)that affects plant phosphorus(P)uptake.Methods:Root PA and classical root functional traits were investigated for 21 coexisting species in a deciduous broad-leaved forest in warm temperate-subtropical transition zone,China.We analyzed the root order variation of absorptive fine root PA,clarified the attribution of root PA in root economic space(RES)and the different P acquisition strategies of co-occurring species based on the multidimensional RES theory,and determined the dominant factors affecting interspecific variation in root PA.Results:There was no distinct pattern of PA variation with root order in the first three root orders of absorptive fine roots,and root PA was constrained by phylogeny.Root PA is a competitive trait affiliated with the conservation gradient in RES.The tight linkages among root PA,mycorrhizal colonization,diameter,specific root length,and nitrogen concentration suggested trade-offs among P acquisition strategies of co-occurring species,i.e.species with long and fine roots acquire inorganic P by actively exploring the soil and secreting phosphatase to mineralize and hydrolyze organic P,while species with short and thick roots obtain P mainly by investing C in mycorrhizal partners.Conclusions:Collectively,our study provides an insight into the forest species coexistence in climatic transition zones,i.e.species coexistence mechanisms based on diverse phosphorus acquisition strategies.展开更多
BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively p...BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively participate.MicroRNAs(miRNAs)are commonly secreted from exosomes for cell communication.Though the regulation of miR-103 on insulin sensitivity has been reported,the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices.AIM To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods.METHODS The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control.The effect of miR-103 on NASH progression was also explored by antagonizing miR-103,including steatosis and inflammation degree changes.The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog(PTEN)was confirmed by dual-luciferase reporter assay.The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells.Finally,the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments.RESULTS The expression of miR-103 was increased in NASH mice,compared to the control,and inhibition of miR-103 could alleviate NASH.The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN.MiR-103-anta decreased p-AMPKa,p-mammalian target of rapamycin(mTOR),and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice.Similar results were also observed in NASH-like cells,and further experiments showed PTEN silencing inhibited the effect of miR-103-anta.AT derivedexosome miR-103 aggravated NASH and increased the expressions of p-AMPKa,p-mTOR,and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice.CONCLUSION AT derived-exosome increased the levels of miR-103 in the liver,and miR-103 aggravated NASH.Mechanically,miR-103 could interact with PTEN and inhibit autophagy.展开更多
BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is func...BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic gastrointestinal disorder characterized by inflammation and ulceration,representing a significant predisposition to colorectal cancer.Recent advances in single-cell RNA se...BACKGROUND Ulcerative colitis(UC)is a chronic gastrointestinal disorder characterized by inflammation and ulceration,representing a significant predisposition to colorectal cancer.Recent advances in single-cell RNA sequencing(scRNA-seq)technology offer a promising avenue for dissecting the complex cellular interactions and molecular signatures driving UC pathology.AIM To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.METHODS In this research,we integrated and analyzed the scRNA-seq data from UC patients.Moreover,we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.RESULTS In this study,we identified the sustained upregulation of inflammatory response pathways during UC progression,characterized the features of damaged endothelial cells in colitis.Furthermore,we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)has a negative correlation with signal transducer and activator of transcription 3.Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC.This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.CONCLUSION The findings suggest that LHPP may serve as a potential therapeutic target for UC,emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.展开更多
BACKGROUND Transient hyperphosphatasemia(TH)is a condition characterized by elevated serum alkaline phosphatase(ALP)in the clinical setting with no evidence of bone or liver disease among children under the age of 5.T...BACKGROUND Transient hyperphosphatasemia(TH)is a condition characterized by elevated serum alkaline phosphatase(ALP)in the clinical setting with no evidence of bone or liver disease among children under the age of 5.Typically,it will resolve spontaneously in a few months in the majority of cases.TH has been found to be associated with viral infections.Two cases of TH associated with coronavirus disease 2019(COVID-19)infection in toddlers have been previously reported.CASE SUMMARY A previously healthy 2-year-old boy presented with fever and positive real-time polymerase chain reaction for COVID-19.Prior to his illness,the patient had been in close contact with his grandfather,who later developed COVID-19.The physical examination on admission was unremarkable.He remained asymptomatic throughout 7 d of hospitalization.On the 5th day of his illness,blood tests showed markedly elevated serum ALP(4178 U/L).Results from the simultaneous testing of the remaining liver profiles and metabolic bone panels were normal.Two months after discharge from the hospital,the patient continued to thrive well.The skeletal surveys revealed no significant abnormalities.The serum ALP declined into the normal range adjusted for his age.This evidence is consistent with the diagnosis of TH.CONCLUSION TH can occur in COVID-19-infected toddlers.Serial measurements of ALP levels have been shown to gradually decline into the normal range within a few months.Therefore,being aware of this transient abnormality will help clinicians to avoid additional unnecessary investigations.展开更多
文摘BACKGROUND The incidence of primary liver cancer is increasing year by year.In 2022 alone,more than 900000 people were diagnosed with liver cancer worldwide,with hepatocellular carcinoma(HCC)accounting for 75%-85%of cases.HCC is the most common primary liver cancer.China has the highest incidence and mortality rate of HCC in the world,and it is one of the malignant tumors that seriously threaten the health of Chinese people.The onset of liver cancer is occult,the early cases lack typical clinical symptoms,and most of the patients are already in the middle and late stage when diagnosed.Therefore,it is very important to find new markers for the early detection and diagnosis of liver cancer,improve the therapeutic effect,and improve the prognosis of patients.Protein tyrosine phosphatase non-receptor 2(PTPN2)has been shown to be associated with colorectal cancer,triple-negative breast cancer,non-small cell lung cancer,and prostate cancer,but its biological role and function in tumors remain to be further studied.AIM To combine the results of relevant data obtained from The Cancer Genome Atlas(TCGA)to provide the first in-depth analysis of the biological role of PTPN2 in HCC.METHODS The expression of PTPN2 in HCC was first analyzed based on the TCGA database,and the findings were then verified by immunohistochemical staining,quantitative real-time polymerase chain reaction(qRT-PCR),and immunoblotting.The value of PTPN2 in predicting the survival of patients with HCC was assessed by analyzing the relationship between PTPN2 expression in HCC tissues and clinicopathological features.Finally,the potential of PTPN2 affecting immune escape of liver cancer was evaluated by tumor immune dysfunction and exclusion and immunohistochemical staining.RESULTS The results of immunohistochemical staining,qRT-PCR,and immunoblotting in combination with TCGA database analysis showed that PTPN2 was highly expressed and associated with a poor prognosis in HCC patients.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that PTPN2 was associated with various pathways,including cancer-related pathways,the Notch signaling pathway,and the MAPK signaling pathway.Gene Set Enrichment Analysis showed that PTPN2 was highly expressed in various immune-related pathways,such as the epithelial mesenchymal transition process.A risk model score based on PTPN2 showed that immune escape was significantly enhanced in the high-risk group compared with the low-risk group.CONCLUSION This study investigated PTPN2 from multiple biological perspectives,revealing that PTPN2 can function as a biomarker of poor prognosis and mediate immune evasion in HCC.
基金This work was supported by grants from the National Key Research and Development Program of China(2021YFF1000500)the Open Competition Program of Ten Major Directions of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province,China(2022SDZG07)+3 种基金the Key Areas Research and Development Programs of Guangdong Province,China(2022B0202060005)the STICGrantof China(SGDX20210823103535007)the Major Program of Guangdong Basic and Applied Research,China(2019B030302006)the Natural Science Foundation of Guangdong Province,China(2021A1515010826and 2020A1515110261).
文摘Bacteria play critical roles in regulating soil phosphorus(P) cycling. The effects of interactions between crops and soil P-availability on bacterial communities and the feedback regulation of soil P cycling by the bacterial community modifications are poorly understood. Here, six soybean(Glycine max) genotypes with differences in P efficiency were cultivated in acidic soils with long-term sufficient or deficient P-fertilizer treatments. The acid phosphatase(AcP) activities, organic-P concentrations and associated bacterial community compositions were determined in bulk and rhizosphere soils. The results showed that both soybean plant P content and the soil AcP activity were negatively correlated with soil organic-P concentration in P-deficient acidic soils. Soil P-availability affected the ɑ-diversity of bacteria in both bulk and rhizosphere soils. However, soybean had a stronger effect on the bacterial community composition, as reflected by the similar biomarker bacteria in the rhizosphere soils in both P-treatments. The relative abundance of biomarker bacteria Proteobacteria was strongly correlated with soil organic-P concentration and AcP activity in low-P treatments. Further high-throughput sequencing of the phoC gene revealed an obvious shift in Proteobacteria groups between bulk soils and rhizosphere soils, which was emphasized by the higher relative abundances of Cupriavidus and Klebsiella, and lower relative abundance of Xanthomonas in rhizosphere soils. Among them, Cupriavidus was the dominant phoC bacterial genus, and it was negatively correlated with the soil organic-P concentration. These findings suggest that soybean growth relies on organic-P mineralization in P-deficient acidic soils, which might be partially achieved by recruiting specific phoCharboring bacteria, such as Cupriavidus.
基金Yunnan Province High-level Scientific and Technological Talents and Innovation Team Selection Special,No.202405AC350067Basic Research Joint Special General Project of Yunnan Provincial Local Universities(Part),No.202301BA070001-029 and No.202301BA070001-044+1 种基金Scientific Research Fund Project of Education Department of Yunnan Province,No.2023J0926The 8th Research Project of Education and Teaching Reform of Dali University(Special Medical Education Reform Project),No.2022JGYX08-01 and No.2022JGYX08-02.
文摘BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high incidence worldwide.As a common local treatment,RFA has attracted much attention for its efficacy and influence on liver function.AIM To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA.METHODS The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected.The chi-square test was used to compare the data between groups.The Kaplan-Meier method and Cox regression were used to analyze the associ-ations between serum ALP and GGT levels and overall survival,progression-free survival(PFS)and clinical characteristics of patients before treatment.RESULTS The 1-year survival rates of patients with normal(≤135 U/L)and abnormal(>135 U/L)serum ALP before treatment were 91%and 79%,respectively;the 2-year survival rates were 90%and 68%,respectively;and the 5-year survival rates were 35%and 18%,respectively.The difference between the two groups was statistically significant(P=0.01).Before treatment,the 1-year survival rates of patients with normal serum GGT levels(≤45 U/L)and abnormal serum GGT levels(>45 U/L)were 95%and 87%,the 2-year survival rates were 85%and 71%,and the 5-year survival rates were 37%and 21%,respectively.The difference between the two groups was statist-ically significant(P<0.001).Serum ALP[hazard ratio(HR)=1.766,95%confidence interval(95%CI):1.068-2.921,P=0.027]and GGT(HR=2.312,95%CI:1.367-3.912,P=0.002)is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor.The 1-year PFS rates were 72%and 50%,the 2-year PFS rates were 52%and 21%,and the 5-year PFS rates were 14%and 3%,respectively.The difference between the two groups was statistically significant(P<0001).The 1-year PFS rates were 81%and 56%in patients with normal and abnormal serum GGT levels before treatment,respectively;the 2-year PFS rates were 62%and 35%,respectively;and the 5-year PFS rates were 18%and 7%,respectively,with statistical significance between the two groups(P<0.001).The serum ALP concentration(HR=1.653,95%CI:1.001-2.729,P=0.049)and GGT(HR=1.949,95%CI:1.296-2.930,P=0.001)was closely associated with PFS after RFA in patients with PLC.The proportion of male patients with abnormal ALP levels is high,the Child-Pugh grade of liver function is poor,and the incidence of ascites is high.Among GGT-abnormal patients,the Child-Pugh grade of liver function was poor,the tumor stage was late,the proportion of patients with tumors≥5 cm was high,and the incidence of hepatic encephalopathy was high.CONCLUSION Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA,and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.
基金supported by Research Start-up Funding of Shenzhen Traditional Chinese Medicine Hospital,No.2021-07(to FB)Sanming Project of Medicine in Shenzhen,No.SZZYSM 202111011(to XDQ and FB)+1 种基金Key Discipline Established by Zhejiang Province,Jiaxing City Jointly-Pain Medicine,No.2019-ss-ttyx(to LSX)Jiaxing Key Laboratory of Neurology and Pain Medicine,No.[2014]81(to LSX)。
文摘Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.
基金supported by the National Natural Science Foundation of China,Nos.81501048(to JD),81801236(to ZMX),81974189(to HLT)Shanghai 6th People’s Hospital Research Fund,No.ynlc201808(to JD).
文摘Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.
基金financially supported by the National Natural Science Foundation of China(Nos.32230067,32001171 and 32001120)。
文摘Background:The diversity of resource acquisition strategies of plant roots determines the species coexistence patterns to a certain extent.However,few root physiological traits have been investigated,such as root phosphatase activity(PA)that affects plant phosphorus(P)uptake.Methods:Root PA and classical root functional traits were investigated for 21 coexisting species in a deciduous broad-leaved forest in warm temperate-subtropical transition zone,China.We analyzed the root order variation of absorptive fine root PA,clarified the attribution of root PA in root economic space(RES)and the different P acquisition strategies of co-occurring species based on the multidimensional RES theory,and determined the dominant factors affecting interspecific variation in root PA.Results:There was no distinct pattern of PA variation with root order in the first three root orders of absorptive fine roots,and root PA was constrained by phylogeny.Root PA is a competitive trait affiliated with the conservation gradient in RES.The tight linkages among root PA,mycorrhizal colonization,diameter,specific root length,and nitrogen concentration suggested trade-offs among P acquisition strategies of co-occurring species,i.e.species with long and fine roots acquire inorganic P by actively exploring the soil and secreting phosphatase to mineralize and hydrolyze organic P,while species with short and thick roots obtain P mainly by investing C in mycorrhizal partners.Conclusions:Collectively,our study provides an insight into the forest species coexistence in climatic transition zones,i.e.species coexistence mechanisms based on diverse phosphorus acquisition strategies.
基金the Natural Science Foundation of Zhejiang Province,No.LZ21H030002。
文摘BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively participate.MicroRNAs(miRNAs)are commonly secreted from exosomes for cell communication.Though the regulation of miR-103 on insulin sensitivity has been reported,the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices.AIM To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods.METHODS The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control.The effect of miR-103 on NASH progression was also explored by antagonizing miR-103,including steatosis and inflammation degree changes.The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog(PTEN)was confirmed by dual-luciferase reporter assay.The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells.Finally,the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments.RESULTS The expression of miR-103 was increased in NASH mice,compared to the control,and inhibition of miR-103 could alleviate NASH.The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN.MiR-103-anta decreased p-AMPKa,p-mammalian target of rapamycin(mTOR),and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice.Similar results were also observed in NASH-like cells,and further experiments showed PTEN silencing inhibited the effect of miR-103-anta.AT derivedexosome miR-103 aggravated NASH and increased the expressions of p-AMPKa,p-mTOR,and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice.CONCLUSION AT derived-exosome increased the levels of miR-103 in the liver,and miR-103 aggravated NASH.Mechanically,miR-103 could interact with PTEN and inhibit autophagy.
基金Supported by This work was supported by the Natural Science Foundation of Gansu Province,China,No.17JR5RA272 and No.22JR5RA923the Research Fund Project of The First Hospital of Lanzhou University,No.ldyyyn2021-120,No.ldyyyn2020-98 and No.ldyyyn2021-30.
文摘BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.
基金Science and Technology Programme of Traditional Chinese Medicine in Zhejiang Province,No.2023ZF114.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic gastrointestinal disorder characterized by inflammation and ulceration,representing a significant predisposition to colorectal cancer.Recent advances in single-cell RNA sequencing(scRNA-seq)technology offer a promising avenue for dissecting the complex cellular interactions and molecular signatures driving UC pathology.AIM To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.METHODS In this research,we integrated and analyzed the scRNA-seq data from UC patients.Moreover,we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.RESULTS In this study,we identified the sustained upregulation of inflammatory response pathways during UC progression,characterized the features of damaged endothelial cells in colitis.Furthermore,we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)has a negative correlation with signal transducer and activator of transcription 3.Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC.This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.CONCLUSION The findings suggest that LHPP may serve as a potential therapeutic target for UC,emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.
文摘BACKGROUND Transient hyperphosphatasemia(TH)is a condition characterized by elevated serum alkaline phosphatase(ALP)in the clinical setting with no evidence of bone or liver disease among children under the age of 5.Typically,it will resolve spontaneously in a few months in the majority of cases.TH has been found to be associated with viral infections.Two cases of TH associated with coronavirus disease 2019(COVID-19)infection in toddlers have been previously reported.CASE SUMMARY A previously healthy 2-year-old boy presented with fever and positive real-time polymerase chain reaction for COVID-19.Prior to his illness,the patient had been in close contact with his grandfather,who later developed COVID-19.The physical examination on admission was unremarkable.He remained asymptomatic throughout 7 d of hospitalization.On the 5th day of his illness,blood tests showed markedly elevated serum ALP(4178 U/L).Results from the simultaneous testing of the remaining liver profiles and metabolic bone panels were normal.Two months after discharge from the hospital,the patient continued to thrive well.The skeletal surveys revealed no significant abnormalities.The serum ALP declined into the normal range adjusted for his age.This evidence is consistent with the diagnosis of TH.CONCLUSION TH can occur in COVID-19-infected toddlers.Serial measurements of ALP levels have been shown to gradually decline into the normal range within a few months.Therefore,being aware of this transient abnormality will help clinicians to avoid additional unnecessary investigations.
