BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality worldwide.Early detection of HCC is crucial,yet challenging.AIM To investigate the role of dyn...BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality worldwide.Early detection of HCC is crucial,yet challenging.AIM To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio(APR)in hepatitis B progression to HCC.METHODS Data from 4843 patients with hepatitis B(January 2015 to January 2024)were analyzed.HCC incidence rates in males and females were compared using the log-rank test.Data were evaluated using Kaplan–Meier analysis.The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time.Furthermore,Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk.RESULTS The incidence of HCC was higher in males.To ensure the model’s normality assumption,this study applied a logarithmic transformation to APR,yielding ratio.Ratio levels were higher in females(t=5.26,P<0.01).A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males(95%CI:1.653-2.431)and a 2.273-fold higher risk in females(95%CI:1.620-3.190).CONCLUSION Males are more prone to HCC,while females have higher APR levels.Despite no baseline APR link,rising APR indicates a higher HCC risk.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy,with its pathogenesis involving dysregulation of multiple genes,including adenomatous polyposis coli and p53.Emerging evidence suggests that ...BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy,with its pathogenesis involving dysregulation of multiple genes,including adenomatous polyposis coli and p53.Emerging evidence suggests that microRNA 195(miR195)plays a critical role in carcinogenesis by modulating the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway through phosphatase and tensin homologue(PTEN),thereby influencing cellular metabolism.Loss of PTEN function leads to hyperactivation of PI3K/AKT signaling pathway,resulting in upregulated expression of lactate dehydrogenase-5(LDH-5)and promoting the tumor progression.AIM To explore the clinical relevance of miR195,LDH-5,and PTEN expression patterns in CRC patient tissues and their association with clinicopathological features and prognosis.METHODS We enrolled 53 CRC patients who received surgical resection at our hospital from January 2020 to February 2022.Fresh tumor tissues and paired adjacent normal tissues(>5 cm from the tumor margin)were collected.The mRNA expression of miR195 was quantified by real-time quantitative polymerase chain reaction,while the protein expression of LDH-5 and PTEN were assessed via immunohistochemistry.Differences in molecular expression between tumor and adjacent normal tissues were compared,along with their correlations with clinicopathological parameters and prognosis.RESULTS The positive rate of miR195 in CRC tissues(35.85%)was significantly lower than that in adjacent normal tissues(90.57%).LDH-5 displayed a higher positive rate(79.25%)in the tissues compared to normal tissues(11.32%),while PTEN expression was markedly reduced in tumors(28.30%vs 94.34%,P<0.05).Elevated expression of miR195 was observed in CRC tissues from patients with earlier tumor,node,metastasis(TNM)stages and without lymph node metastasis.Conversely,higher expression of LDH-5 was associated with advanced TNM stages,lower differentiation grades,and the presence of lymph node metastasis.Additionally,PTEN expression was higher in patients with smaller tumor diameters and no lymph node metastasis(P<0.05).In CRC tissues,miR195 showed a negative correlation with LDH-5(r=-0.883,P=0.015)but a positive correlation with PTEN(r=0.429,P=0.006).LDH-5 was negatively associated with PTEN(r=-0.396,P<0.001).Patients with miR195 positivity,LDH-5 negativity,and PTEN positivity demonstrated significantly better prognosis(P<0.05).CONCLUSION Low miR195 and PTEN expression,coupled high LDH-5 expression could constitutes a hallmark molecular signature of CRC progression.These signature may act as potential markers for diagnosis and disease assessment,and prognostic evaluation in CRC patients,eventually improving CRC management.展开更多
BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rec...BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.展开更多
This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase(PDP)in malignant tumors and its potential mechanisms.Recent research on tumor metabolic mechanisms has shown that...This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase(PDP)in malignant tumors and its potential mechanisms.Recent research on tumor metabolic mechanisms has shown that PDP dysregulation is closely linked to metabolic reprogramming in tumor cells,and potentially promotes tumor.Research has comprehensively explored the structural-functional characteristics of PDP,its metabolic regulatory mechanisms,and its role in various types of malignant tumors.Nevertheless,several questions still exist regarding its potential mechanisms within acetylation,phosphorylation,hypoxia,immune infiltration,mitochondrial metabolism,drug resistance,oxidative phosphorylation,and tumor prognosis.This article intends to summarize the latest research,examine PDP’s potential as a therapeutic target,and propose future research directions to enhance cancer treatment strategies.展开更多
Objective:To investigate the mechanism by which advanced glycation end products(AGEs)promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growt...Objective:To investigate the mechanism by which advanced glycation end products(AGEs)promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growth factor receptor(EGFR)pathway.Methods:Animal experiments and in vitro cell experiments were conducted using Western blot analysis and tissue cell staining to detect the expression of relevant proteins and cellular morphological changes.Results:AGEs disrupt the SHP1/SHP2 balance,activate the EGFR and TGFβpathways,and promote fibrosis in diabetic nephropathy.Conclusion:AGEs regulate the balance of tyrosine phosphatases SHP1/SHP2,activate the EGFR-mediated signaling pathway,promote the release of inflammatory factors,and ultimately lead to fibrosis in diabetic nephropathy through a novel mechanism.展开更多
In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers ar...In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers are presented with respect to the article by Li et al published in ninth issue of the World Journal of Gastrointestinal Oncology.PTPN2 is a member of the protein tyrosine phosphatase family of signaling proteins that play crucial roles in the regulation of inflammation and immunity.Accordingly,early findings highlighted the contribution of PTPN2 to the pathogenesis of inflammatory and autoimmune disorders related to its dysfunction.On the other hand,recent studies have indicated that PTPN2 has many different roles in different cancer types,which is associated with the complexity of its regulatory network.PTPN2 dephosphorylates and inactivates EGFR,SRC family kinases,JAK1 and JAK3,and STAT1,STAT3,and STAT5 in cell type-and context-dependent manners,which indicates that PTPN2 can perform either prooncogenic or anti-oncogenic functions depending on the tumor subtype.While PTPN2 has been suggested as a potential therapeutic target in cancer treatment,to the best of ourknowledge,no clear treatment protocol has referred to PTPN2.Although there are only few studies that investigated PTPN2 expression in the GI system cancers,which is a potential limitation,the association of this protein with tumor behavior and the influence of PTPN2 on many therapy-related signaling pathways emphasize that PTPN2 could serve as a new molecular biomarker to predict tumor behavior and as a target for therapeutic intervention against GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic potential of PTPN2 in GI tumors,especially in tumors resistant to therapy.展开更多
Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals,including humans(Montoya and Liesenfeld,2004).It occurs worldwide and can persist for a lifetime in mammals.Humans get infecte...Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals,including humans(Montoya and Liesenfeld,2004).It occurs worldwide and can persist for a lifetime in mammals.Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite.In immune-competent individuals,T.展开更多
Hydrolysis of organic phosphorus(P) by soil phosphatases is an important process of P cycling in terrestrial ecosystems, significantly affected by nitrogen(N) and/or P fertilization. However, how soil acid phosphatase...Hydrolysis of organic phosphorus(P) by soil phosphatases is an important process of P cycling in terrestrial ecosystems, significantly affected by nitrogen(N) and/or P fertilization. However, how soil acid phosphatase(ACP) and alkaline phosphatase(ALP) activities respond to N and/or P fertilization and how these responses vary with climatic regions, ecosystem types, and fertilization management remain unclear. This knowledge gap hinders our ability to assess P cycling and availability from a global perspective. We performed a meta-analysis to evaluate the global patterns of soil ACP and ALP activities in response to N and/or P addition. We also examined how climatic regions(arctic to tropical), ecosystem types(cropland, grassland, and forest), and fertilization management(experiment duration and fertilizer type and application rate) affected changes in soil phosphatases after fertilization. It was shown that N fertilizer resulted in 10.1% ± 2.9% increase in soil ACP activity but a minimal effect on soil ALP activity. In contrast, P fertilizer resulted in 7.7% ± 2.6% decrease in soil ACP activity but a small increase in soil ALP activity. The responses of soil ACP and ALP activities to N and/or P fertilization were largely consistent across climatic regions but varied with ecosystem types and fertilization management, and the effects of ecosystem types and fertilization management were enzyme-dependent. Random forest analysis identified climate(mean annual precipitation and temperature) and change in soil pH as the key factors explaining variations in soil ACP and ALP activities. Therefore, N input and ecosystem types should be explicitly disentangled when assessing terrestrial P cycling.展开更多
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
Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overa...Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.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
Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated durin...Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown.This study tested the hypothesis that progesterone(P4)and/or interferon tau(IFNT)regulate TNSALP activity during pregnancy in sheep.Methods In Exp.1,ewes were bred and received daily intramuscular injections of either corn oil vehicle(CO)or 25 mg progesterone in CO(P4)for the first 8 days of pregnancy and were hysterectomized on either Day 9,12,or 125 of gestation.In Exp.2,ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist(RU486)in CO from Days 8 to 15,and twice daily intrauterine injections of either control proteins(CX)or IFNT(25μg/uterine horn/d)from Days 11 to 15(treatment groups:P4+CX;P4+IFNT;RU486+P4+CX;and RU486+P4+IFNT)and were hysterectomized on Day 16.Results In Exp.1,endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12.TNSALP activity appeared greater in the epithelia,stratum compactum stroma,and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12.On Day 125,TNSALP activity localized to uterine epithelial and endothelial cells,independent of P4 treatment.TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes.In Exp.2,endometrial homogenates from ewes administered RU486+P4+CX had lower TNSALP activity those for P4+CX and P4+IFNT ewes.Immunoreactive TNSALP protein appeared greater in the mid-and deep-glandular epithelia in RU486+P4+CX treated ewes as compared to the other treatment groups.Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486+P4+CX compared to the other treatment groups.Conclusions These results suggest that P4,but not IFNT,regulates the expression and activity of TNSALP in uteroplacental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.展开更多
Leaf acid phosphatase (APase) activities of 274 soybean genotypes were surveyed under field conditions with two levels of P supplies, and a nutrient solution culture experiment with eight selected genotypes was subseq...Leaf acid phosphatase (APase) activities of 274 soybean genotypes were surveyed under field conditions with two levels of P supplies, and a nutrient solution culture experiment with eight selected genotypes was subsequently conducted under greenhouse conditions to further characterize APase activity and its isoform expression induced by P starvation. Results from the field experiment showed that there was a great genotypic variation for leaf APase activity among the tested soybean genotypes from different origins, and APase activity in many of the tested genotypes (about 60%) was generally increased in the treatment without P fertilizer addition. Results from the nutrient solution culture experiment showed that APase activity in all the eight tested genotypes was generally enhanced by P starvation. Six isoforms of APases were detected in isoelectric focusing gels with samples from both young and old leaves. The activity of all the six isoforms was increased by P starvation, but no new APase isoform was induced. Our results suggest that leaf APase activity could serve as an enzymatic indicator of P starvation for soybean; the increase in leaf APase activity under low P stress was mainly caused by the increase in the activity of existing isoforms but not by the induction of new isoforms.展开更多
BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dict...BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dictates that is essential.METHODS Through Gene Expression Profiling Interactive Analysis,we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues.For detecting the mRNA expression of RBM5,quantitative real time-polymerase chain reaction was performed.Protein expression levels of RBM5,hexokinase 2,lactate dehydrogenase A,phosphatase and tensin homolog(PTEN),phosphoinositide 3-kinase(PI3K),phosphorylated-protein kinase B(p-AKT),and AKT were determined via Western blot.Functionally,cell counting kit-8 and 5-ethynyl-2’-deoxyuridine(EDU)assay were performed to evaluate proliferation of CRC cells.Invasiveness and migration of CRC cells were evaluated through conducting transwell assays.Glucose consumption,lactate production and adenosinetriphosphate(ATP)production were measured through a glucose assay kit,a lactate assay kit and an ATP production assay kit,respectively.Besides,RNA immunoprecipitation assay,half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN.To establish a xenotypic tumor mice,CRC cells were subcutaneously injected into the right flank of each mouse.Protein expression of RBM5,Ki67,and PTEN in tumor tissues was examined using immunohistochemistry staining.Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.RESULTS We discovered down-regulation of RBM5 expression in CRC tissues and cells.RBM5 overexpression repressed proliferation,migration and invasion of CRC cells.Meantime,RBM5 impaired glycolysis in CRC cells,presenting as decreased glucose consumption,decreased lactate production and decreased ATP production.Besides,RBM5 bound to PTEN mRNA to stabilize its expression.PTEN expression was positively regulated by RBM5 in CRC cells.The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression.The suppressive influences of RBM5 on glycolysis,proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown.RBM5 suppressed tumor growth and liver metastasis in vivo.CONCLUSION This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN,expanding the importance of RBM5 in the treatment of CRC.展开更多
The distribution of acid phosphatase activity in nucellar cells of wheat ( Triticum aestivum L.) during degeneration has been studied using the lead precipitation method at the electron microscopic level. Acid phos...The distribution of acid phosphatase activity in nucellar cells of wheat ( Triticum aestivum L.) during degeneration has been studied using the lead precipitation method at the electron microscopic level. Acid phosphatase was localized in the slightly condensed nuclear chromatin in nucellar cells without any sign of ultrastructural degeneration. As the nucellar cells started degenerating, the enzyme activity in the cell was observed, in the order from small vacuoles to cell walls, mitochondria, plastids and endoplasmic reticulum. Enzyme activity was the highest in most components of the nucellar cells adjacent to the embryo sac where the degeneration of nucellar cells was the strongest, but it was not observed in the nuclei of the degenerated nucellar cells. The results indicated that the degeneration of nucellar cells was a progressive and orderly process and supported that the degeneration of nucellar cells was a programmed cell death.展开更多
[Objective]The activities of urease and phosphatase in integrated vertical flow constructed wetland and purification effect of black and malodorous river were studied.[Method]Honeycomb stone and soft filler were used ...[Objective]The activities of urease and phosphatase in integrated vertical flow constructed wetland and purification effect of black and malodorous river were studied.[Method]Honeycomb stone and soft filler were used as matrix,the biological grid integrated vertical flow constructed wetland system was built to strengthen treatment for black and malodorous river,and the activities of urease and phosphatase of two fillers in different functional areas of constructed wetland were tested to study the film formation property of two fillers in different functional areas.[Result]Both urease and phosphatase activities on biofilm of soft filler were significantly higher than on biofilm of honeycomb stone filler;indicating that choosing soft filler was more advantageous to the growth of biofilm;and urease activity had significant correlation with total nitrogen removal rate,while phosphatase activity had no significant correlation with total phosphorus removal rate.[Conclusion]This study provided evidences for utilizing the activities of urease and phosphatase to evaluate the purification effect of black and malodorous river and choose appropriate filler.展开更多
[Object] The study aimed to supply a reference for evaluating ecotoxicology of soil contaminated with phthalate acid esters(PAEs).[Method] The dynamic effects of DBP and DEHP on activities and kinetics parameters of u...[Object] The study aimed to supply a reference for evaluating ecotoxicology of soil contaminated with phthalate acid esters(PAEs).[Method] The dynamic effects of DBP and DEHP on activities and kinetics parameters of urease and phosphatase in agro-soil contaminated artificially with DBP and DEHP were studied.[Result] The activities of urease and phosphatase were both inhibited significantly by higher contents of DBP and DEHP in soils compared with CK.The inhabitations increased with increasing DBP and DEHP c...展开更多
Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cement...Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.展开更多
Due to their toxicity,the increased distribution of microcystins(MCs) has become an important worldwide problem.MCs have been recognized as inhibitors of protein phosphatase 2A(PP2A) through their binding to the PP2A ...Due to their toxicity,the increased distribution of microcystins(MCs) has become an important worldwide problem.MCs have been recognized as inhibitors of protein phosphatase 2A(PP2A) through their binding to the PP2A catalytic subunit.However,the exact mechanism of MC toxicity has not been elucidated,especially concerning the cellular response and its autoregulation.To further dissect the role of PP2A in MC-induced toxicity,the present study was undertaken to determine the response of PP2A in human amniotic epithelial(FL) cells treated with microcystin-LR(MCLR),one of the MC congeners.The results show that a low-dose treatment of MCLR in FL cells for 6 h induced an increase in PP2A activity,and a high-dose treatment of MCLR for 24 h decreased the activity of PP2A,as expected.The increased mRNA and protein levels of the PP2A C subunit may explain the increased activity of PP2A.Furthermore,MCLR altered microtubule post-translational modifications through PP2A.These results further clarify the underlying mechanism how MCLR affects PP2A and may be helpful for elucidating the complex toxicity of MCLR.展开更多
文摘BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality worldwide.Early detection of HCC is crucial,yet challenging.AIM To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio(APR)in hepatitis B progression to HCC.METHODS Data from 4843 patients with hepatitis B(January 2015 to January 2024)were analyzed.HCC incidence rates in males and females were compared using the log-rank test.Data were evaluated using Kaplan–Meier analysis.The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time.Furthermore,Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk.RESULTS The incidence of HCC was higher in males.To ensure the model’s normality assumption,this study applied a logarithmic transformation to APR,yielding ratio.Ratio levels were higher in females(t=5.26,P<0.01).A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males(95%CI:1.653-2.431)and a 2.273-fold higher risk in females(95%CI:1.620-3.190).CONCLUSION Males are more prone to HCC,while females have higher APR levels.Despite no baseline APR link,rising APR indicates a higher HCC risk.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy,with its pathogenesis involving dysregulation of multiple genes,including adenomatous polyposis coli and p53.Emerging evidence suggests that microRNA 195(miR195)plays a critical role in carcinogenesis by modulating the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway through phosphatase and tensin homologue(PTEN),thereby influencing cellular metabolism.Loss of PTEN function leads to hyperactivation of PI3K/AKT signaling pathway,resulting in upregulated expression of lactate dehydrogenase-5(LDH-5)and promoting the tumor progression.AIM To explore the clinical relevance of miR195,LDH-5,and PTEN expression patterns in CRC patient tissues and their association with clinicopathological features and prognosis.METHODS We enrolled 53 CRC patients who received surgical resection at our hospital from January 2020 to February 2022.Fresh tumor tissues and paired adjacent normal tissues(>5 cm from the tumor margin)were collected.The mRNA expression of miR195 was quantified by real-time quantitative polymerase chain reaction,while the protein expression of LDH-5 and PTEN were assessed via immunohistochemistry.Differences in molecular expression between tumor and adjacent normal tissues were compared,along with their correlations with clinicopathological parameters and prognosis.RESULTS The positive rate of miR195 in CRC tissues(35.85%)was significantly lower than that in adjacent normal tissues(90.57%).LDH-5 displayed a higher positive rate(79.25%)in the tissues compared to normal tissues(11.32%),while PTEN expression was markedly reduced in tumors(28.30%vs 94.34%,P<0.05).Elevated expression of miR195 was observed in CRC tissues from patients with earlier tumor,node,metastasis(TNM)stages and without lymph node metastasis.Conversely,higher expression of LDH-5 was associated with advanced TNM stages,lower differentiation grades,and the presence of lymph node metastasis.Additionally,PTEN expression was higher in patients with smaller tumor diameters and no lymph node metastasis(P<0.05).In CRC tissues,miR195 showed a negative correlation with LDH-5(r=-0.883,P=0.015)but a positive correlation with PTEN(r=0.429,P=0.006).LDH-5 was negatively associated with PTEN(r=-0.396,P<0.001).Patients with miR195 positivity,LDH-5 negativity,and PTEN positivity demonstrated significantly better prognosis(P<0.05).CONCLUSION Low miR195 and PTEN expression,coupled high LDH-5 expression could constitutes a hallmark molecular signature of CRC progression.These signature may act as potential markers for diagnosis and disease assessment,and prognostic evaluation in CRC patients,eventually improving CRC management.
基金This study was reviewed and approved by the Ethic Committee of Medical College of Henan Vocational University of Science and Technology(Approval No.HVUYL414101416920231017001)all participants signed a written informed consent.
文摘BACKGROUND Centromere protein A(CENPA)exhibits an increased expression level in primary human rectal cancer tissues,but its role has not been investigated.AIM To clarify the specific role and mechanism of CENPA in rectal cancer progression.METHODS CENPA protein expression in rectal cancer tissues and cell lines were detected.CENPA was overexpressed and knocked down in SW837 and SW480 cells,and proliferation,invasion,apoptosis and epithelial-mesenchymal transition(EMT)marker protein levels were examined.O6-methylguanine DNA methyltransferase(MGMT)promoter methylation was assessed with methylation-specific poly-merase chain reaction.Co-immunoprecipitation assay verified the interaction between MGMT and protein tyrosine phosphatase nonreceptor type 4(PTPN4).SW837 cells with CENPA knockdown were injected subcutaneously into mice,and tumor growth was examined.RESULTS CENPA was upregulated in rectal cancer tissues and cell lines.CENPA overex-pression promoted proliferation,invasion and EMT,and inhibited apoptosis in rectal cancer cells.Whereas CENPA knockdown showed the opposite results.Moreover,CENPA inhibited MGMT expression by promoting DNA methyltrans-ferase 1-mediated MGMT promoter methylation.MGMT knockdown abolished the CENPA knockdown-mediated inhibition of rectal cancer cell progression.MGMT increased PTPN4 protein stability by inhibiting PTPN4 ubiquitination degradation via competing with ubiquitin-conjugating enzyme E2O for interacting with PTPN4.PTPN4 knockdown abolished the inhibitory effects of MGMT overexpression on rectal cancer cell progression.Moreover,CENPA knockdown inhibited xenograft tumor growth in vivo.CONCLUSION CENPA knockdown inhibited rectal cancer cell growth and attenuated xenograft tumor growth through regulating the MGMT/PTPN4 axis.
基金funded by National Social Science Foundation if Gansu Province(24JRRA694)Scientific and Technological Development Guiding Plan Project of Lanzhou City(2023-ZD-62,2024-9-52)GanSu Health Industry Planning Project(GSWSKY2024-51).
文摘This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase(PDP)in malignant tumors and its potential mechanisms.Recent research on tumor metabolic mechanisms has shown that PDP dysregulation is closely linked to metabolic reprogramming in tumor cells,and potentially promotes tumor.Research has comprehensively explored the structural-functional characteristics of PDP,its metabolic regulatory mechanisms,and its role in various types of malignant tumors.Nevertheless,several questions still exist regarding its potential mechanisms within acetylation,phosphorylation,hypoxia,immune infiltration,mitochondrial metabolism,drug resistance,oxidative phosphorylation,and tumor prognosis.This article intends to summarize the latest research,examine PDP’s potential as a therapeutic target,and propose future research directions to enhance cancer treatment strategies.
基金Baoding Municipal Science and Technology Plan Project(Project No.:2441ZF089)。
文摘Objective:To investigate the mechanism by which advanced glycation end products(AGEs)promote diabetic kidney disease fibrosis by regulating the tyrosine phosphatase SHP1/SHP2 balance and activating the epidermal growth factor receptor(EGFR)pathway.Methods:Animal experiments and in vitro cell experiments were conducted using Western blot analysis and tissue cell staining to detect the expression of relevant proteins and cellular morphological changes.Results:AGEs disrupt the SHP1/SHP2 balance,activate the EGFR and TGFβpathways,and promote fibrosis in diabetic nephropathy.Conclusion:AGEs regulate the balance of tyrosine phosphatases SHP1/SHP2,activate the EGFR-mediated signaling pathway,promote the release of inflammatory factors,and ultimately lead to fibrosis in diabetic nephropathy through a novel mechanism.
文摘In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers are presented with respect to the article by Li et al published in ninth issue of the World Journal of Gastrointestinal Oncology.PTPN2 is a member of the protein tyrosine phosphatase family of signaling proteins that play crucial roles in the regulation of inflammation and immunity.Accordingly,early findings highlighted the contribution of PTPN2 to the pathogenesis of inflammatory and autoimmune disorders related to its dysfunction.On the other hand,recent studies have indicated that PTPN2 has many different roles in different cancer types,which is associated with the complexity of its regulatory network.PTPN2 dephosphorylates and inactivates EGFR,SRC family kinases,JAK1 and JAK3,and STAT1,STAT3,and STAT5 in cell type-and context-dependent manners,which indicates that PTPN2 can perform either prooncogenic or anti-oncogenic functions depending on the tumor subtype.While PTPN2 has been suggested as a potential therapeutic target in cancer treatment,to the best of ourknowledge,no clear treatment protocol has referred to PTPN2.Although there are only few studies that investigated PTPN2 expression in the GI system cancers,which is a potential limitation,the association of this protein with tumor behavior and the influence of PTPN2 on many therapy-related signaling pathways emphasize that PTPN2 could serve as a new molecular biomarker to predict tumor behavior and as a target for therapeutic intervention against GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic potential of PTPN2 in GI tumors,especially in tumors resistant to therapy.
基金supported by the National Natural Sci ence Foundation of China(No.31672543)the Zhejiang Province“Sannongliufang”Science and Technology Coopera tion Project(No.2020SNLF007),China.
文摘Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals,including humans(Montoya and Liesenfeld,2004).It occurs worldwide and can persist for a lifetime in mammals.Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite.In immune-competent individuals,T.
基金financial support from the Strategic Priority Research Program of Chinese Academy of Sciences(Nos.XDA23070202 and XDB40020000)the National Natural Science Foundation of China(Nos.41977068 and 41977105)the Programs of Chinese Academy of Sciences(No.QYZDB-SSW-DQC039)。
文摘Hydrolysis of organic phosphorus(P) by soil phosphatases is an important process of P cycling in terrestrial ecosystems, significantly affected by nitrogen(N) and/or P fertilization. However, how soil acid phosphatase(ACP) and alkaline phosphatase(ALP) activities respond to N and/or P fertilization and how these responses vary with climatic regions, ecosystem types, and fertilization management remain unclear. This knowledge gap hinders our ability to assess P cycling and availability from a global perspective. We performed a meta-analysis to evaluate the global patterns of soil ACP and ALP activities in response to N and/or P addition. We also examined how climatic regions(arctic to tropical), ecosystem types(cropland, grassland, and forest), and fertilization management(experiment duration and fertilizer type and application rate) affected changes in soil phosphatases after fertilization. It was shown that N fertilizer resulted in 10.1% ± 2.9% increase in soil ACP activity but a minimal effect on soil ALP activity. In contrast, P fertilizer resulted in 7.7% ± 2.6% decrease in soil ACP activity but a small increase in soil ALP activity. The responses of soil ACP and ALP activities to N and/or P fertilization were largely consistent across climatic regions but varied with ecosystem types and fertilization management, and the effects of ecosystem types and fertilization management were enzyme-dependent. Random forest analysis identified climate(mean annual precipitation and temperature) and change in soil pH as the key factors explaining variations in soil ACP and ALP activities. Therefore, N input and ecosystem types should be explicitly disentangled when assessing terrestrial P cycling.
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supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY21H080005)the National Natural Science Foundation of China(Nos.81572920 and 82100171).
文摘Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.
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 Agriculture and Food Research Initiative Competitive Grant 2016–67015-24958 from the USDA National Institute of Food and Agriculture。
文摘Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown.This study tested the hypothesis that progesterone(P4)and/or interferon tau(IFNT)regulate TNSALP activity during pregnancy in sheep.Methods In Exp.1,ewes were bred and received daily intramuscular injections of either corn oil vehicle(CO)or 25 mg progesterone in CO(P4)for the first 8 days of pregnancy and were hysterectomized on either Day 9,12,or 125 of gestation.In Exp.2,ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist(RU486)in CO from Days 8 to 15,and twice daily intrauterine injections of either control proteins(CX)or IFNT(25μg/uterine horn/d)from Days 11 to 15(treatment groups:P4+CX;P4+IFNT;RU486+P4+CX;and RU486+P4+IFNT)and were hysterectomized on Day 16.Results In Exp.1,endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12.TNSALP activity appeared greater in the epithelia,stratum compactum stroma,and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12.On Day 125,TNSALP activity localized to uterine epithelial and endothelial cells,independent of P4 treatment.TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes.In Exp.2,endometrial homogenates from ewes administered RU486+P4+CX had lower TNSALP activity those for P4+CX and P4+IFNT ewes.Immunoreactive TNSALP protein appeared greater in the mid-and deep-glandular epithelia in RU486+P4+CX treated ewes as compared to the other treatment groups.Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486+P4+CX compared to the other treatment groups.Conclusions These results suggest that P4,but not IFNT,regulates the expression and activity of TNSALP in uteroplacental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.
文摘Leaf acid phosphatase (APase) activities of 274 soybean genotypes were surveyed under field conditions with two levels of P supplies, and a nutrient solution culture experiment with eight selected genotypes was subsequently conducted under greenhouse conditions to further characterize APase activity and its isoform expression induced by P starvation. Results from the field experiment showed that there was a great genotypic variation for leaf APase activity among the tested soybean genotypes from different origins, and APase activity in many of the tested genotypes (about 60%) was generally increased in the treatment without P fertilizer addition. Results from the nutrient solution culture experiment showed that APase activity in all the eight tested genotypes was generally enhanced by P starvation. Six isoforms of APases were detected in isoelectric focusing gels with samples from both young and old leaves. The activity of all the six isoforms was increased by P starvation, but no new APase isoform was induced. Our results suggest that leaf APase activity could serve as an enzymatic indicator of P starvation for soybean; the increase in leaf APase activity under low P stress was mainly caused by the increase in the activity of existing isoforms but not by the induction of new isoforms.
文摘BACKGROUND RNA binding motif 5(RBM5)has emerged as crucial regulators in many cancers.AIM To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer(CRC)dictates that is essential.METHODS Through Gene Expression Profiling Interactive Analysis,we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues.For detecting the mRNA expression of RBM5,quantitative real time-polymerase chain reaction was performed.Protein expression levels of RBM5,hexokinase 2,lactate dehydrogenase A,phosphatase and tensin homolog(PTEN),phosphoinositide 3-kinase(PI3K),phosphorylated-protein kinase B(p-AKT),and AKT were determined via Western blot.Functionally,cell counting kit-8 and 5-ethynyl-2’-deoxyuridine(EDU)assay were performed to evaluate proliferation of CRC cells.Invasiveness and migration of CRC cells were evaluated through conducting transwell assays.Glucose consumption,lactate production and adenosinetriphosphate(ATP)production were measured through a glucose assay kit,a lactate assay kit and an ATP production assay kit,respectively.Besides,RNA immunoprecipitation assay,half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN.To establish a xenotypic tumor mice,CRC cells were subcutaneously injected into the right flank of each mouse.Protein expression of RBM5,Ki67,and PTEN in tumor tissues was examined using immunohistochemistry staining.Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.RESULTS We discovered down-regulation of RBM5 expression in CRC tissues and cells.RBM5 overexpression repressed proliferation,migration and invasion of CRC cells.Meantime,RBM5 impaired glycolysis in CRC cells,presenting as decreased glucose consumption,decreased lactate production and decreased ATP production.Besides,RBM5 bound to PTEN mRNA to stabilize its expression.PTEN expression was positively regulated by RBM5 in CRC cells.The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression.The suppressive influences of RBM5 on glycolysis,proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown.RBM5 suppressed tumor growth and liver metastasis in vivo.CONCLUSION This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN,expanding the importance of RBM5 in the treatment of CRC.
文摘The distribution of acid phosphatase activity in nucellar cells of wheat ( Triticum aestivum L.) during degeneration has been studied using the lead precipitation method at the electron microscopic level. Acid phosphatase was localized in the slightly condensed nuclear chromatin in nucellar cells without any sign of ultrastructural degeneration. As the nucellar cells started degenerating, the enzyme activity in the cell was observed, in the order from small vacuoles to cell walls, mitochondria, plastids and endoplasmic reticulum. Enzyme activity was the highest in most components of the nucellar cells adjacent to the embryo sac where the degeneration of nucellar cells was the strongest, but it was not observed in the nuclei of the degenerated nucellar cells. The results indicated that the degeneration of nucellar cells was a progressive and orderly process and supported that the degeneration of nucellar cells was a programmed cell death.
基金Supported by National Major Science and Technology Projects(2009ZX07317-006)National Major Science and Technology Projects(2009ZX07317-009)~~
文摘[Objective]The activities of urease and phosphatase in integrated vertical flow constructed wetland and purification effect of black and malodorous river were studied.[Method]Honeycomb stone and soft filler were used as matrix,the biological grid integrated vertical flow constructed wetland system was built to strengthen treatment for black and malodorous river,and the activities of urease and phosphatase of two fillers in different functional areas of constructed wetland were tested to study the film formation property of two fillers in different functional areas.[Result]Both urease and phosphatase activities on biofilm of soft filler were significantly higher than on biofilm of honeycomb stone filler;indicating that choosing soft filler was more advantageous to the growth of biofilm;and urease activity had significant correlation with total nitrogen removal rate,while phosphatase activity had no significant correlation with total phosphorus removal rate.[Conclusion]This study provided evidences for utilizing the activities of urease and phosphatase to evaluate the purification effect of black and malodorous river and choose appropriate filler.
基金Supported by the Blue Project of Jiangsu ProvinceNatural Science Foundation of Huai an(SN0777)+1 种基金the Development Project of Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around HongzeLake(HZHL0813)Natural Science Foundation of Huaiyin Institute of Technology(351707077)~~
文摘[Object] The study aimed to supply a reference for evaluating ecotoxicology of soil contaminated with phthalate acid esters(PAEs).[Method] The dynamic effects of DBP and DEHP on activities and kinetics parameters of urease and phosphatase in agro-soil contaminated artificially with DBP and DEHP were studied.[Result] The activities of urease and phosphatase were both inhibited significantly by higher contents of DBP and DEHP in soils compared with CK.The inhabitations increased with increasing DBP and DEHP c...
基金supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) and extramural NIH funding(JLM-DE12889 and AR53102)
文摘Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.
基金Project supported by the National Natural Science Foundation of China (Nos. 30771827 and 20777067)the Key Special Program on the S & T of China for the Pollution Control and Treatment of Water Bodies (No. 2008ZX07421-001)
文摘Due to their toxicity,the increased distribution of microcystins(MCs) has become an important worldwide problem.MCs have been recognized as inhibitors of protein phosphatase 2A(PP2A) through their binding to the PP2A catalytic subunit.However,the exact mechanism of MC toxicity has not been elucidated,especially concerning the cellular response and its autoregulation.To further dissect the role of PP2A in MC-induced toxicity,the present study was undertaken to determine the response of PP2A in human amniotic epithelial(FL) cells treated with microcystin-LR(MCLR),one of the MC congeners.The results show that a low-dose treatment of MCLR in FL cells for 6 h induced an increase in PP2A activity,and a high-dose treatment of MCLR for 24 h decreased the activity of PP2A,as expected.The increased mRNA and protein levels of the PP2A C subunit may explain the increased activity of PP2A.Furthermore,MCLR altered microtubule post-translational modifications through PP2A.These results further clarify the underlying mechanism how MCLR affects PP2A and may be helpful for elucidating the complex toxicity of MCLR.
