AIM: To assess blood chitinase 3-like 1(CHi3L1) levels for 2 mo after minimally invasive colorectal resection(MICR) for colorectal cancer(CRC). METHODS: CRC patients in an Institutional Review Board approved data/plas...AIM: To assess blood chitinase 3-like 1(CHi3L1) levels for 2 mo after minimally invasive colorectal resection(MICR) for colorectal cancer(CRC). METHODS: CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative(PreO p), early postoperative(PostO p), and 1 or more late PostO p samples [postoperative day(POD) 7-27] available were included. Plasma CHi3L1 levels(ng/m L) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS: PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL(n = 80). Significantly elevated(P < 0.001) median plasma levels(ng/mL) over PreOp levels were detected on POD1(667.7 CI: 495.7, 771.7; n = 79), POD 3(132.6 CI: 95.5, 173.7; n = 76), POD7-13(96.4 CI: 67.7, 136.9; n = 62), POD14-20(101.4 CI: 80.7, 287.4; n = 22), and POD 21-27(98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.展开更多
Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Me...Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Methods:Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B(CHB)patients.Significant fibrosis was defined as a liver stiffness>9.7 kPa.The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic(ROC)analysis.Results:Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis(≥F2)than in those without significant hepatic fibrosis(<F2)(56.5 ng/mL vs.81.9 ng/mL,P<0.001).In CHB patients,the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6%and 59.1%,respectively,with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728(95%CI:0.637–0.820).Conclusions:Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis.Moreover,CHI3L1 is feasible in monitoring disease progression.展开更多
AIM To identify whether chitinase 3-like 1(CHI3 L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma(ESCC) and to analyze this protein's cellular source.METHODS An ELISA was c...AIM To identify whether chitinase 3-like 1(CHI3 L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma(ESCC) and to analyze this protein's cellular source.METHODS An ELISA was conducted to detect the concentration of CHI3 L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3 L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed,and fluorescent staining was utilized to explore the cellular origins of CHI3 L1. We stimulated monocyte-derived macrophages(MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3 L1 by q PCR and ELISA.RESULTS The level of serum CHI3 L1 was higher in older patients(≥ 60) than in patients under the age of 60(P = 0.001). The patients with higher levels of CHI3 L1 had a significantly shorter overall survival,whereas the traditional markers,carcinoembryonic antigen and squamous cell carcinoma antigen,were less effective(P > 0.05). A multivariate Cox analysis(P = 0.001) indicated that CHI3 L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3 L1. Interleukin-6(IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3 L1. The serum concentration of CHI3 L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil(NEU,P = 0.045),neutrophil/lymphocyte rate(NLR,P = 0.016),and C-reactive protein(CRP,P < 0.001).CONCLUSION Our study first established a connection between the pretreated CHI3 L1 and patients with ESCC,and the serum CHI3 L1 was primarily secreted by ESCC-surrounded macrophages.展开更多
Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulati...Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.展开更多
5-Aminolevulinic acid(ALA)can inhibit abscisic acid(ABA)-induced stomatal closure.However,the molecular mechanism is unclear.In this study,we found that ALA upregulated the MdPP2AC expression and PP2A activity in the ...5-Aminolevulinic acid(ALA)can inhibit abscisic acid(ABA)-induced stomatal closure.However,the molecular mechanism is unclear.In this study,we found that ALA upregulated the MdPP2AC expression and PP2A activity in the apple(Malus domestica Borkh.cv.‘Fuji’)leaves.With the promoter of MdPP2AC as bait,a diacylglycerol kinase MdDGK3-like was selected by the Yeast One Hybrid(Y1H)from the cDNA library of the epidermis of apple leaves treated by exogenous ALA.Additional to binding the promoter of MdPP2AC,MdDGK3-like was found to inhibit the transcription activity of MdPP2AC promoter,while ALA significantly eliminated the role of MdDGK3-like.In tobacco leaves,MdDGK3-like was localized in the nucleus of stomatal guard cells.Therefore,MdDGK3-like might act as a transcription factor negatively regulating MdPP2AC expression and causing stomatal closure.To further identify MdDGK3-like functions,several transiently transgenic apple leaves(including overexpression and interference)were established.The results revealed that overexpression of MdDGK3-like promoted stomatal closure by increasing Ca^(2+)and H_(2)O_(2)and decreasing flavonol levels in the guard cells.Conversely,MdDGK3-like(i)led the stomatal opening with lower levels of Ca^(2+)and H_(2)O_(2)but higher flavonols.Based on these,we proposed a new hypothesis that ALA up-regulated MdPP2AC expression via negatively regulating the expression of MdDGK3-like to up-regulate PP2A expression and the enzyme activity,which improved the stomatal aperture.Since it was the first time that MdDGK3-like was showed to act as a transcription factor,the proposed model provided a new insight onto the mechanisms of ALA-induced stomatal opening.展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
Potassium(K^(+)),an essential macronutrient,strongly influences myriad fundamental processes,while its deficiency inhibits plant growth.Jasmonic acid(JA)regulates plant growth;however,its role in plant growth inhibiti...Potassium(K^(+)),an essential macronutrient,strongly influences myriad fundamental processes,while its deficiency inhibits plant growth.Jasmonic acid(JA)regulates plant growth;however,its role in plant growth inhibition under K^(+)deficiency remains nebulous.Herein,we determined that JA significantly inhibits low K^(+)tolerance and K^(+)uptake in tomato.Methyl jasmonate treatment induced the expression of SlMYC3-like under low K^(+)stress,which bound the promoters of the genes that encode KT/KUP/HAK-type transporter(SlHAK5)and voltage-gated K^(+)channel(SILKT1)and inhibited their expression.Knockdown of SlMYC3-like enhanced low K^(+)stress tolerance and decreased JA responses,while its overexpression led to low K^(+)stress sensitivity and promoted jasmonate responses in tomato.In addition,jasmonate ZIM-domain transcriptional repressor 2/3(SlJAZ2/3)interacted with SlMYC3-like;this interaction decreased DNA-binding activity of SlMYC3-like.SlMYC3-like promoted SlJAZ2/3 expression,forming a negative feedback circuit in JA signaling.Silencing SlJAZ2/3 increased plant susceptibility to low K^(+)stress.Our findings demonstrate the involvement of the JA–SlJAZ2/3–SlMYC3-like module in K^(+)uptake and plant growth in tomato under low K^(+)stress,providing novel insights into the regulation of plant growth and K^(+)uptake.展开更多
Chitinase-3-like protein 1(CHI3L1)is part of the glycoside hydrolase family 18.Despite lacking enzymatic activity,its unique structure allows it to bind to ligands,altering its steric configuration to mediate cell pro...Chitinase-3-like protein 1(CHI3L1)is part of the glycoside hydrolase family 18.Despite lacking enzymatic activity,its unique structure allows it to bind to ligands,altering its steric configuration to mediate cell proliferation,inflammation,fibrosis,and carcinogenesis.In liver disease,CHI3L1 serves as a common diagnostic biomarker for hepatitis-related fibrosis.Additionally,CHI3L1 can predict the risk of non-alcoholic steatohepatitis,the progression of hepatic fibrosis,and the prognosis of alcoholic liver disease and hepatocellular carcinoma.It also aids in diagnosing and staging non-alcoholic fatty liver disease-related and alcoholic liver disease-related fibrosis,and in monitoring hepatitis-related fibrosis treatment.Furthermore,CHI3L1 is secreted by various cells,including hepatocytes,hepatic stellate cells,macrophages,and mesenchymal stem cells,to regulate hepatic injury,fibrosis,steatosis,and hepatocellular carcinoma through different signaling pathways.This review highlights CHI3L1's dual roles as both a biomarker and regulator in various liver diseases,aiming to broaden researchers'understanding of its potential applications.展开更多
目的探讨慢性乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝病患者血清壳多糖酶3样蛋白1(chitosan 3-like protein 1,CHI3L1)水平与γ-谷氨酰转肽酶/血小板比值(GPR)和天冬氨酸氨基转移酶/血小板比值(APRI)的相关性及诊断价值。方法...目的探讨慢性乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝病患者血清壳多糖酶3样蛋白1(chitosan 3-like protein 1,CHI3L1)水平与γ-谷氨酰转肽酶/血小板比值(GPR)和天冬氨酸氨基转移酶/血小板比值(APRI)的相关性及诊断价值。方法将纳入的慢性HBV感染者221例,分为慢性乙型肝炎(CHB,n=49)、肝硬化(LC,n=132)和原发性肝癌(PHC,n=40)3组。分别检测血清CHI3L1、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(γ-GGT)和血小板(PLT),计算GPR及APRI。结果①PHC组年龄、CHI3L1、γ-GGT、GPR及APRI显著高于CHB组(P<0.05),ALT、PLT显著降低(P<0.05);PHC组AST、γ-GGT、GPR及APRI显著高于LC组(P<0.05)。②CHI3L1诊断CHB、LC和PHC的AUC分别为0.748(95%CI:0.640~0.856)、0.933(95%CI:0.896~0.971)和0.928(95%CI:0.860~0.997);GPR诊断CHB、LC和PHC的AUC分别为0.852(95%CI:0.767~0.938)、0.945(95%CI:0.912~0.978)和0.992(95%CI:0.980~1.000);APRI诊断CH组、LC和PHC的AUC分别为0.665(9%CI:0.543~0.786)、0.737(95%CI:0.661~0.813)和0.893(95%CI:0.811~0.974)。③Spearman相关性分析表明,3组患者CHI3L1与GPR、APRI均呈正相关(P<0.05)。结论CHB组、LC组和PHC组中的CHI3L1与GPR的相关性明显优于CHI3L1与APRI的相关性,可用GPR来替代CHI3L1预测肝脏的病变程度。展开更多
基金Supported by Mr.Wade Thompson and family donation funds to the Divisions of Colon and Rectal surgery,Department of Surgery,Mount Sinai West Hospital,New York,NY 10019
文摘AIM: To assess blood chitinase 3-like 1(CHi3L1) levels for 2 mo after minimally invasive colorectal resection(MICR) for colorectal cancer(CRC). METHODS: CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative(PreO p), early postoperative(PostO p), and 1 or more late PostO p samples [postoperative day(POD) 7-27] available were included. Plasma CHi3L1 levels(ng/m L) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS: PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL(n = 80). Significantly elevated(P < 0.001) median plasma levels(ng/mL) over PreOp levels were detected on POD1(667.7 CI: 495.7, 771.7; n = 79), POD 3(132.6 CI: 95.5, 173.7; n = 76), POD7-13(96.4 CI: 67.7, 136.9; n = 62), POD14-20(101.4 CI: 80.7, 287.4; n = 22), and POD 21-27(98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.
基金the Research Ethics Committee of The First Affiliated Hospital of Zhejiang University School of Medicine(No.2018-918).
文摘Background:Serum chitinase-3-like protein 1(CHI3L1)is a potential biomarker for fibrosis assessment.We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virusrelated fibrosis.Methods:Serum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B(CHB)patients.Significant fibrosis was defined as a liver stiffness>9.7 kPa.The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic(ROC)analysis.Results:Serum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis(≥F2)than in those without significant hepatic fibrosis(<F2)(56.5 ng/mL vs.81.9 ng/mL,P<0.001).In CHB patients,the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6%and 59.1%,respectively,with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728(95%CI:0.637–0.820).Conclusions:Serum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis.Moreover,CHI3L1 is feasible in monitoring disease progression.
文摘AIM To identify whether chitinase 3-like 1(CHI3 L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma(ESCC) and to analyze this protein's cellular source.METHODS An ELISA was conducted to detect the concentration of CHI3 L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3 L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed,and fluorescent staining was utilized to explore the cellular origins of CHI3 L1. We stimulated monocyte-derived macrophages(MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3 L1 by q PCR and ELISA.RESULTS The level of serum CHI3 L1 was higher in older patients(≥ 60) than in patients under the age of 60(P = 0.001). The patients with higher levels of CHI3 L1 had a significantly shorter overall survival,whereas the traditional markers,carcinoembryonic antigen and squamous cell carcinoma antigen,were less effective(P > 0.05). A multivariate Cox analysis(P = 0.001) indicated that CHI3 L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3 L1. Interleukin-6(IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3 L1. The serum concentration of CHI3 L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil(NEU,P = 0.045),neutrophil/lymphocyte rate(NLR,P = 0.016),and C-reactive protein(CRP,P < 0.001).CONCLUSION Our study first established a connection between the pretreated CHI3 L1 and patients with ESCC,and the serum CHI3 L1 was primarily secreted by ESCC-surrounded macrophages.
基金financially supported grants from National Natural Science Foundation of China(Grant Nos.31902053,31870279,31730081)China Postdoctoral Science Foundation(Grant No.2018M642273)+3 种基金Jiangsu Planned Projects or Postdoctoral Reaearch Funds(Grant No.2019K169)the Fundamental Research Funds for the Central Uniersities(Grant No.KYQN202031)the National Key Research and Development Program of China(Grant Nos.2019YFD1001500,2020YFD1000400)the earmarked fund for Jiangsu Agricultural Industry Technology System,and a project funded by the Priority academic Program Development of Jiangsu Higher Education Institutions。
文摘Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.
基金supported by the National Natural Science Foundation of China(Grant No.32172512)the Jiangsu Special Fund for Frontier Foundation Research of Carbon Peaking and Carbon Neutralization(Grant No.BK20220005)+1 种基金Jiangsu Agricultural Science and Technology Innovation Fund[Grant No.CX(20)2023]a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘5-Aminolevulinic acid(ALA)can inhibit abscisic acid(ABA)-induced stomatal closure.However,the molecular mechanism is unclear.In this study,we found that ALA upregulated the MdPP2AC expression and PP2A activity in the apple(Malus domestica Borkh.cv.‘Fuji’)leaves.With the promoter of MdPP2AC as bait,a diacylglycerol kinase MdDGK3-like was selected by the Yeast One Hybrid(Y1H)from the cDNA library of the epidermis of apple leaves treated by exogenous ALA.Additional to binding the promoter of MdPP2AC,MdDGK3-like was found to inhibit the transcription activity of MdPP2AC promoter,while ALA significantly eliminated the role of MdDGK3-like.In tobacco leaves,MdDGK3-like was localized in the nucleus of stomatal guard cells.Therefore,MdDGK3-like might act as a transcription factor negatively regulating MdPP2AC expression and causing stomatal closure.To further identify MdDGK3-like functions,several transiently transgenic apple leaves(including overexpression and interference)were established.The results revealed that overexpression of MdDGK3-like promoted stomatal closure by increasing Ca^(2+)and H_(2)O_(2)and decreasing flavonol levels in the guard cells.Conversely,MdDGK3-like(i)led the stomatal opening with lower levels of Ca^(2+)and H_(2)O_(2)but higher flavonols.Based on these,we proposed a new hypothesis that ALA up-regulated MdPP2AC expression via negatively regulating the expression of MdDGK3-like to up-regulate PP2A expression and the enzyme activity,which improved the stomatal aperture.Since it was the first time that MdDGK3-like was showed to act as a transcription factor,the proposed model provided a new insight onto the mechanisms of ALA-induced stomatal opening.
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
基金supported by the National Natural Science Foundation of China(Grant Nos.32272716,31991184,and 32172548)the National Key Research and Development Program of China(Grant No.2022YFF1003002)+1 种基金Science and Technology Program of Liaoning Province(Grant No.2022020768-JH1/102-02)the earmarked fund for CARS(Grant No.CARS-23).
文摘Potassium(K^(+)),an essential macronutrient,strongly influences myriad fundamental processes,while its deficiency inhibits plant growth.Jasmonic acid(JA)regulates plant growth;however,its role in plant growth inhibition under K^(+)deficiency remains nebulous.Herein,we determined that JA significantly inhibits low K^(+)tolerance and K^(+)uptake in tomato.Methyl jasmonate treatment induced the expression of SlMYC3-like under low K^(+)stress,which bound the promoters of the genes that encode KT/KUP/HAK-type transporter(SlHAK5)and voltage-gated K^(+)channel(SILKT1)and inhibited their expression.Knockdown of SlMYC3-like enhanced low K^(+)stress tolerance and decreased JA responses,while its overexpression led to low K^(+)stress sensitivity and promoted jasmonate responses in tomato.In addition,jasmonate ZIM-domain transcriptional repressor 2/3(SlJAZ2/3)interacted with SlMYC3-like;this interaction decreased DNA-binding activity of SlMYC3-like.SlMYC3-like promoted SlJAZ2/3 expression,forming a negative feedback circuit in JA signaling.Silencing SlJAZ2/3 increased plant susceptibility to low K^(+)stress.Our findings demonstrate the involvement of the JA–SlJAZ2/3–SlMYC3-like module in K^(+)uptake and plant growth in tomato under low K^(+)stress,providing novel insights into the regulation of plant growth and K^(+)uptake.
基金supported by the National Key R&D Program of China(No.2022YFA1303804).
文摘Chitinase-3-like protein 1(CHI3L1)is part of the glycoside hydrolase family 18.Despite lacking enzymatic activity,its unique structure allows it to bind to ligands,altering its steric configuration to mediate cell proliferation,inflammation,fibrosis,and carcinogenesis.In liver disease,CHI3L1 serves as a common diagnostic biomarker for hepatitis-related fibrosis.Additionally,CHI3L1 can predict the risk of non-alcoholic steatohepatitis,the progression of hepatic fibrosis,and the prognosis of alcoholic liver disease and hepatocellular carcinoma.It also aids in diagnosing and staging non-alcoholic fatty liver disease-related and alcoholic liver disease-related fibrosis,and in monitoring hepatitis-related fibrosis treatment.Furthermore,CHI3L1 is secreted by various cells,including hepatocytes,hepatic stellate cells,macrophages,and mesenchymal stem cells,to regulate hepatic injury,fibrosis,steatosis,and hepatocellular carcinoma through different signaling pathways.This review highlights CHI3L1's dual roles as both a biomarker and regulator in various liver diseases,aiming to broaden researchers'understanding of its potential applications.
文摘目的探讨慢性乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝病患者血清壳多糖酶3样蛋白1(chitosan 3-like protein 1,CHI3L1)水平与γ-谷氨酰转肽酶/血小板比值(GPR)和天冬氨酸氨基转移酶/血小板比值(APRI)的相关性及诊断价值。方法将纳入的慢性HBV感染者221例,分为慢性乙型肝炎(CHB,n=49)、肝硬化(LC,n=132)和原发性肝癌(PHC,n=40)3组。分别检测血清CHI3L1、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(γ-GGT)和血小板(PLT),计算GPR及APRI。结果①PHC组年龄、CHI3L1、γ-GGT、GPR及APRI显著高于CHB组(P<0.05),ALT、PLT显著降低(P<0.05);PHC组AST、γ-GGT、GPR及APRI显著高于LC组(P<0.05)。②CHI3L1诊断CHB、LC和PHC的AUC分别为0.748(95%CI:0.640~0.856)、0.933(95%CI:0.896~0.971)和0.928(95%CI:0.860~0.997);GPR诊断CHB、LC和PHC的AUC分别为0.852(95%CI:0.767~0.938)、0.945(95%CI:0.912~0.978)和0.992(95%CI:0.980~1.000);APRI诊断CH组、LC和PHC的AUC分别为0.665(9%CI:0.543~0.786)、0.737(95%CI:0.661~0.813)和0.893(95%CI:0.811~0.974)。③Spearman相关性分析表明,3组患者CHI3L1与GPR、APRI均呈正相关(P<0.05)。结论CHB组、LC组和PHC组中的CHI3L1与GPR的相关性明显优于CHI3L1与APRI的相关性,可用GPR来替代CHI3L1预测肝脏的病变程度。
