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@#Abstract: Objective To explore the correlation between the levels of silent information regulator 1 (SIRT1) and forkhead box protein O3 (FOXO3) in peripheral blood mononuclear cells of patients with active pulmonary tuberculosis (APTB) and macrophage-related cytokines-inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Methods A total of 64 APTB patients who were treated in Yubei Hospital, the First Affiliated Hospital of Chongqing Medical University from January 2020 to December 2021 were gathered as the APTB group, 59 people with latent tuberculosis infection (LTBI) were gathered as the LTBI group, and 62 healthy people were gathered as the control group. Quantitative real-time PCR (qPCR) method was performed to measure the levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells. The enzyme-linked immunosorbent assay (ELISA) was performed to measure serum iNOS and Arg-1 levels; ROC curve was used to analyze the value of SIRT1 mRNA and FOXO3 mRNA levels in the differential diagnosis of LTBI and APTB; Pearson correlation was performed to analyze the correlation of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients with serum iNOS and Arg-1 levels. Results The levels of SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells decreased in control group, LTBI group and APTB group, and the level of serum Arg-1 increased in turn (P<0.05). The AUCs of SIRT1 mRNA and FOXO3 mRNA in differential diagnosis of LTBI and APTB were 0.876 and 0.887, respectively, the sensitivity was 71.2% and 76.3%, and the specificity was 96.9% and 90.6% respectively. The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients were positively correlated (r=0.500, P<0.05), and they were positively correlated with serum iNOS and negatively correlated with serum Arg-1 (P<0.05). The SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells of APTB patients after 6 months of treatment were higher than those before treatment, and serum Arg-1 was lower than before treatment (P<0.05). Conclusions The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients are low, and they are positively correlated with macrophage-related cytokine iNOS and negatively correlated with Arg-1.
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Objective@#To investigate the potential effects of cytochrome P450 1A1 (CYP1A1) in regulating macrophages polarize to M2 type and explore the molecular mechanism.@*Methods@#All trials were completely randomized. ① Experiment 1: 6-8 weeks old healthy male C57BL/6J mice were collected, and primary peritoneal cells were extracted, then the cells were divided into phosphate buffered saline (PBS) group and interleukin-4 (IL-4) group. The cells in the IL-4 group were stimulated with 10 mg/L IL-4 (M2 macrophage inducer); and those in the PBS group were given with an equal amount of PBS. The mRNA expressions of intracellular M2 type polarized marker molecules including arginase-1 (Arg-1) and chitinase 3 like protein 1 (YM1) at 2, 4, 6 hours after IL-4 challenge were determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The phosphorylation of tyrosine protein kinase 1/signaling transcriptional and transduced activator 6 (JAK1/STAT6) signaling pathway and protein expressions of CYP1A1 and Arg-1 at 6, 12, 24 hours after IL-4 challenge were determined by Western Blot. ② Experiment 2: RAW264.7 cells with high expression CYP1A1 (CYP1A1/RAW) and their negative control cells (NC/RAW) were cultured in vitro. The cells in logarithmic growth phase were collected, and then they were divided into PBS control group and IL-4 group. The treatment method was the same as experiment 1. The phosphorylations of intracellular JAK1/STAT6 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in different cells at 1 hour and 2 hours after IL-4 challenge were determined by Western Blot. The mRNA and protein expressions of Arg-1 in different cells at 2 hours and 4 hours after IL-4 challenge were determined by RT-qPCR and Western Blot, respectively.@*Results@#① Experiment 1: after IL-4 challenge for 2 hours, the mRNA expressions of Arg-1 and YM1 in the primary peritoneal macrophages of mice were significantly increased as compared with the PBS control group [Arg-1 mRNA (2-ΔΔCt): 1.75±0.82 vs. 1.00±0.21; YM1 mRNA (2-ΔΔCt): 2.58±0.53 vs. 1.00±0.20, both P < 0.05] which indicated that IL-4 induced macrophage to M2 type polarization successfully. Meanwhile, the mRNA expression of CYP1A1 in polarized mouse peritoneal primary macrophages was also elevated as compared with the PBS control group, and peaked at 4 hours [CYP1A1 mRNA (2-ΔΔCt): 2.25±0.69 vs. 1.00±0.17, P < 0.01]. The results indicated that CYP1A1 expression was enhanced when macrophages polarized to M2 type. Compared with the PBS control group, the bands of phosphorylated JAK1 (p-JAK1), phosphorylated STAT6 (p-STAT6), Arg-1 and CYP1A1 were enhanced in primary peritoneal macrophages of mice in the IL-4 group, and reached the peak value at 12 hours then gradually decreased. This result indicated that the phosphorylation of JAK1/STAT6 pathway was enhanced in M2 macrophages with high expression of CYP1A1, and the pathway was activated. ② Experiment 2: after IL-4 challenge for 2 hours, the expression of Arg-1 mRNA in CYP1A1/RAW cells was significantly higher than that in NC/RAW cells (2-ΔΔCt: 3.02±0.60 vs. 1.47±0.43, P < 0.05), and the protein band signal was also stronger, and both peaked at 4 hours. This indicated that CYP1A1 could promote the polarization of macrophages to M2. After IL-4 challenge for 2 hours, the expression of p-JAK1 and p-JAK3 protein bands in both cells were significantly enhanced as compared with the PBS control group, but the enhancement of p-STAT6 band in CYP1A1/RAW cells was stronger than that of NC/RAW cells, indicating that CYP1A1 promoted macrophage polarization by promoting phosphorylation of the JAK1/STAT6 pathway. In the meantime, the protein band of Akt, a downstream protein of the PI3K/Akt pathway, in CYP1A1/RAW cells was significantly lower than that of NC/RAW cells, indicating that CYP1A1 did not promote macrophage polarization through this pathway.@*Conclusions@#CYP1A1 promotes the polarization of macrophage to M2 type. The mechanism is related to promoting the phosphorylation of JAK1/STAT6 pathway.
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The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1 were administered to chondrocytes. Micro-CT scanning and histological observations were conducted on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IB, which further reduced the downstream phosphorylation of P65 in nuclear factor-B (NF-B) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1-induced chondrocyte damage. , Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.
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To investigate the potential effects of cytochrome P450 1A1 (CYP1A1) in regulating macrophages polarize to M2 type and explore the molecular mechanism. Methods All trials were completely randomized. ① Experiment 1: 6-8 weeks old healthy male C57BL/6J mice were collected, and primary peritoneal cells were extracted, then the cells were divided into phosphate buffered saline (PBS) group and interleukin-4 (IL-4) group. The cells in the IL-4 group were stimulated with 10 mg/L IL-4 (M2 macrophage inducer); and those in the PBS group were given with an equal amount of PBS. The mRNA expressions of intracellular M2 type polarized marker molecules including arginase-1 (Arg-1) and chitinase 3 like protein 1 (YM1) at 2, 4, 6 hours after IL-4 challenge were determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The phosphorylation of tyrosine protein kinase 1/signaling transcriptional and transduced activator 6 (JAK1/STAT6) signaling pathway and protein expressions of CYP1A1 and Arg-1 at 6, 12, 24 hours after IL-4 challenge were determined by Western Blot. ② Experiment 2: RAW264.7 cells with high expression CYP1A1 (CYP1A1/RAW) and their negative control cells (NC/RAW) were cultured in vitro. The cells in logarithmic growth phase were collected, and then they were divided into PBS control group and IL-4 group. The treatment method was the same as experiment 1. The phosphorylations of intracellular JAK1/STAT6 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in different cells at 1 hour and 2 hours after IL-4 challenge were determined by Western Blot. The mRNA and protein expressions of Arg-1 in different cells at 2 hours and 4 hours after IL-4 challenge were determined by RT-qPCR and Western Blot, respectively. Results ① Experiment 1: after IL-4 challenge for 2 hours, the mRNA expressions of Arg-1 and YM1 in the primary peritoneal macrophages of mice were significantly increased as compared with the PBS control group [Arg-1 mRNA (2-ΔΔCt): 1.75±0.82 vs. 1.00±0.21; YM1 mRNA (2-ΔΔCt): 2.58±0.53 vs. 1.00±0.20, both P < 0.05] which indicated that IL-4 induced macrophage to M2 type polarization successfully. Meanwhile, the mRNA expression of CYP1A1 in polarized mouse peritoneal primary macrophages was also elevated as compared with the PBS control group, and peaked at 4 hours [CYP1A1 mRNA (2-ΔΔCt): 2.25±0.69 vs. 1.00±0.17, P < 0.01]. The results indicated that CYP1A1 expression was enhanced when macrophages polarized to M2 type. Compared with the PBS control group, the bands of phosphorylated JAK1 (p-JAK1), phosphorylated STAT6 (p-STAT6), Arg-1 and CYP1A1 were enhanced in primary peritoneal macrophages of mice in the IL-4 group, and reached the peak value at 12 hours then gradually decreased. This result indicated that the phosphorylation of JAK1/STAT6 pathway was enhanced in M2 macrophages with high expression of CYP1A1, and the pathway was activated. ② Experiment 2: after IL-4 challenge for 2 hours, the expression of Arg-1 mRNA in CYP1A1/RAW cells was significantly higher than that in NC/RAW cells (2-ΔΔCt:3.02±0.60 vs. 1.47±0.43, P < 0.05), and the protein band signal was also stronger, and both peaked at 4 hours. This indicated that CYP1A1 could promote the polarization of macrophages to M2. After IL-4 challenge for 2 hours, the expression of p-JAK1 and p-JAK3 protein bands in both cells were significantly enhanced as compared with the PBS control group, but the enhancement of p-STAT6 band in CYP1A1/RAW cells was stronger than that of NC/RAW cells, indicating that CYP1A1 promoted macrophage polarization by promoting phosphorylation of the JAK1/STAT6 pathway. In the meantime, the protein band of Akt, a downstream protein of the PI3K/Akt pathway, in CYP1A1/RAW cells was significantly lower than that of NC/RAW cells, indicating that CYP1A1 did not promote macrophage polarization through this pathway. Conclusions CYP1A1 promotes the polarization of macrophage to M2 type. The mechanism is related to promoting the phosphorylation of JAK1/STAT6 pathway.
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Viperin is a multifunctional protein that was first identified in human primary macrophages treated with interferon-γ and in human fibroblasts infected with human cytomegalovirus. This protein plays a role as an anti-viral protein and a regulator of cell signaling pathways or cellular metabolism when induced in a variety of cells such as fibroblasts, hepatocytes and immune cells including T cells and dendritic cells. However, the role of viperin in macrophages is unknown. Here, we show that viperin is basally expressed in murine bone marrow cells including monocytes. Its expression is maintained in bone marrow monocyte-derived macrophages (BMDMs) depending on macrophage colony-stimulating factor (M-CSF) treatment but not on granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. In wild type (WT) and viperin knockout (KO) BMDMs differentiated with M-CSF or G-MCSF, there are little differences at the gene expression levels of M1 and M2 macrophage markers such as inducible nitric oxide synthase (iNOS) and arginase-1, and cytokines such as IL-6 and IL-10, indicating that viperin expression in BMDMs does not affect the basal gene expression of macrophage markers and cytokines. However, when BMDMs are completely polarized, the levels of expression of macrophage markers and secretion of cytokines in viperin KO M1 and M2 macrophages are significantly higher than those in WT M1 and M2 macrophages. The data suggest that viperin plays a role as a regulator in polarization of macrophages and secretion of M1 and M2 cytokines.
Subject(s)
Humans , Bone Marrow , Bone Marrow Cells , Cytokines , Cytomegalovirus , Dendritic Cells , Fibroblasts , Gene Expression , Granulocyte-Macrophage Colony-Stimulating Factor , Hepatocytes , Interleukin-10 , Interleukin-6 , Macrophage Colony-Stimulating Factor , Macrophages , Metabolism , Monocytes , Nitric Oxide Synthase Type II , T-LymphocytesABSTRACT
In this study,we compared the serum levels of transforming growth factor-β1 (TGF-β1),interleukin-10 (IL-10),and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-term survival kidney transplant recipients (STSKTRs).We then evaluated the relationship between these levels and graft function.Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs (graft survival approximately 1-3 years post-transplantation).All patients had stable kidney function.The samples were collected at our institution during the patients' follow-up examinations between March 2017 and September 2017.The plasma levels of TGF-β1,IL-10,and arginase-1 were analyzed using enzyme-linked immunosorbent assays (ELISA).The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs.The time elapsed since transplantation was positively correlated with the levels of TGF-β 1 and arginase-1 in the LTSKTRs.The estimated glomerular filtration rate was positively correlated with the TGF-β1 level,and the serum creatinine level was negatively correlated with the TGF-β1 level.Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs,and we found that TGF-β1 was positively correlated with long-term graft survival and function.Additionally,TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation.On the basis of these findings,TGF-β1 and arginase-1 may play important roles in determining long-term graft survival.Thus,we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.
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In this study,we compared the serum levels of transforming growth factor-β1 (TGF-β1),interleukin-10 (IL-10),and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-term survival kidney transplant recipients (STSKTRs).We then evaluated the relationship between these levels and graft function.Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs (graft survival approximately 1-3 years post-transplantation).All patients had stable kidney function.The samples were collected at our institution during the patients' follow-up examinations between March 2017 and September 2017.The plasma levels of TGF-β1,IL-10,and arginase-1 were analyzed using enzyme-linked immunosorbent assays (ELISA).The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs.The time elapsed since transplantation was positively correlated with the levels of TGF-β 1 and arginase-1 in the LTSKTRs.The estimated glomerular filtration rate was positively correlated with the TGF-β1 level,and the serum creatinine level was negatively correlated with the TGF-β1 level.Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs,and we found that TGF-β1 was positively correlated with long-term graft survival and function.Additionally,TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation.On the basis of these findings,TGF-β1 and arginase-1 may play important roles in determining long-term graft survival.Thus,we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.
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Purpose To evaluate the expression of Arginine-1 (Arg-1) and Glypican-3 (GPC-3) in hepatocellular carcinoma (HCC) and non-hepatocellular carcinoma,as well as to summarize the related researches.Methods 156 cases of HCC,5 cases of cholangiocarcinoma,20 cases of metastatic adenocarcinoma and 18 cases of other types of tumors were studied.Immunohistochemical study for Arg-1 and GPC-3 was performed on the formalin-fixed and paraffin-embedded tumor tissues.Results The positive expression rates of Arg-1 in HCC and non-hepatocellular carcinoma were 93.6％ (146/156) and 0 (0/43),respectively,meanwhile the expression rate decreased with decreasing of differentiation (r =-0.264,P =0.001).GPC-3 expression was observed in 141 of 156 cases of HCC (90.4％) and 6 of 43 cases of non-hepatocellular carcinoma (14％),and the expression rate increased with decreasing of differentiation (r =0.179,P =0.026).The sensitivity,specificity,positive predictive value and negative predictive value of Arg-1 and GPC-3 in distinguishing HCC from non-hepatocellular carcinoma were 93.6％,100％,100％,81.1％ and 90.4％,86％,96.0％,71.2％,respectively.Conclusion Arg-1 is a sensitive and specific marker of hepatocytes.The application of Arg-1 and GPC-3 is of great significance in diagnosis of HCC and liver metastatic adenocarcinoma.
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Objective To investigate the curative effect of microwave ablation for non-small cell lung cancer (NSCLC) patients,and to analyze the serum concentration changes of vascular endothelial growth factor (VEGF),arginase-1 (Arg-1),inducible nitric oxide synthase (iNOS) before and after microwave ablation and their correlations.Methods A total of 30 cases of healthy people (control group) and 30 cases of advanced NSCLC (test group) were selected.The serum concentrations of VEGF,Arg-1 and iNOS in control group and test group (before microwave ablation,the first postoperative day,the third postoperative day and the first postoperative month) were measured by enzyme-linked immunosorbent assay (ELISA).Results The effective rate of microwave ablation for advanced NSCLC was 33.3％ (10/30),and the disease control rate was 70.0％ (21/30).The concentrations of VEGF,Arg-1 and iNOS in test group before microwave ablation were (816.56 ± 13.26)pg/ml,(5.17±0.20) ng/ml and (544.18 ± 13.93)pg/ml,which were higher than those in control group (93.43 ± 9.93) pg/ml,(1.08 ± 0.05) ng/ml and (8.08 ± 0.33) pg/ml,and the differences were statistically significant (t =239.093,P ＜ 0.001;t =110.359,P ＜ 0.001;t =210.792,P ＜ 0.001).The concentrations of VEGF were (708.41 ± 10.49) pg/ml,(592.63 ± 7.25) pg/ml and (521.91 ± 8.32) pg/ml on the first day,third day and 1 month after microwave ablation in patients with advanced NSCLC,which were significantly lower than those before treatment (all P ＜ 0.05).The homologous concentrations of Arg-1 were (5.95 ± 0.10) ng/ml,(7.02 ± 0.13) ng/ml and (7.67 ± 0.92) ng/ml,which were significantly higher than those before treatment (all P ＜ 0.05).The homologous concentrations of iNOS were (453.01 ± 9.48) pg/ml,(393.21 ± 9.42) pg/ml and (352.60 ± 8.31) pg/ml,which were significantly lower than those before treatment (all P ＜ 0.05).The expression of iNOS was positively related with VEGF in NSCLC patients before treatment (r =0.379,P =0.039),and the expression of Arg-1 was negatively related with VEGF (r =-0.556,P =0.001).However,the expression of iNOS was not associated with Arg-1 (r =-0.238,P =0.205).Conclusion Microwave ablation is effective for local therapy of NSCLC,which can directly kill cancer cells,and affect the levels of VEGF,Arg-1 and iNOS.VEGF has certain correlation with iNOS and Arg-1,but there was no correlation between iNOS and Arg-1.Microwave ablation can change the tumor microenvironment in a certain extent,and stimulate the body to produce anti-tumor immunity.
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Objective To investigate the curative effect of microwave ablation for non-small cell lung cancer (NSCLC) patients,and to analyze the serum concentration changes of vascular endothelial growth factor (VEGF),arginase-1 (Arg-1),inducible nitric oxide synthase (iNOS) before and after microwave ablation and their correlations.Methods A total of 30 cases of healthy people (control group) and 30 cases of advanced NSCLC (test group) were selected.The serum concentrations of VEGF,Arg-1 and iNOS in control group and test group (before microwave ablation,the first postoperative day,the third postoperative day and the first postoperative month) were measured by enzyme-linked immunosorbent assay (ELISA).Results The effective rate of microwave ablation for advanced NSCLC was 33.3％ (10/30),and the disease control rate was 70.0％ (21/30).The concentrations of VEGF,Arg-1 and iNOS in test group before microwave ablation were (816.56 ± 13.26)pg/ml,(5.17±0.20) ng/ml and (544.18 ± 13.93)pg/ml,which were higher than those in control group (93.43 ± 9.93) pg/ml,(1.08 ± 0.05) ng/ml and (8.08 ± 0.33) pg/ml,and the differences were statistically significant (t =239.093,P ＜ 0.001;t =110.359,P ＜ 0.001;t =210.792,P ＜ 0.001).The concentrations of VEGF were (708.41 ± 10.49) pg/ml,(592.63 ± 7.25) pg/ml and (521.91 ± 8.32) pg/ml on the first day,third day and 1 month after microwave ablation in patients with advanced NSCLC,which were significantly lower than those before treatment (all P ＜ 0.05).The homologous concentrations of Arg-1 were (5.95 ± 0.10) ng/ml,(7.02 ± 0.13) ng/ml and (7.67 ± 0.92) ng/ml,which were significantly higher than those before treatment (all P ＜ 0.05).The homologous concentrations of iNOS were (453.01 ± 9.48) pg/ml,(393.21 ± 9.42) pg/ml and (352.60 ± 8.31) pg/ml,which were significantly lower than those before treatment (all P ＜ 0.05).The expression of iNOS was positively related with VEGF in NSCLC patients before treatment (r =0.379,P =0.039),and the expression of Arg-1 was negatively related with VEGF (r =-0.556,P =0.001).However,the expression of iNOS was not associated with Arg-1 (r =-0.238,P =0.205).Conclusion Microwave ablation is effective for local therapy of NSCLC,which can directly kill cancer cells,and affect the levels of VEGF,Arg-1 and iNOS.VEGF has certain correlation with iNOS and Arg-1,but there was no correlation between iNOS and Arg-1.Microwave ablation can change the tumor microenvironment in a certain extent,and stimulate the body to produce anti-tumor immunity.
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Objective To analyze the relationship between Arg -1 expression and the clinical pathologi-cal factors ,proliferation and prognosis value in patients with colorectal cancer .Methods The expression of Arg-1 was observed in normal tissues ,chronic inflammatory tissues ,and adenomas inflammatory carcinoma tissues of mice.At the same time,Arg-1 expression was observed in human colorectal cancer adjacent tissues ,inflamed tis-sues and colorectal cancer tissues .Arg-1 expressed in 20 cases colorectal inflammation -cancer model in mice . Arg-1 expressed in 20 normal colorectal tissues .Fiftheen colitis tissues and 110 colorectal cancer tissues were examined by Immunohistochemistry .Statistical analysis was used to analyze the changes of Arg -1 expression in different groups of mice and human colon tissue cases .Results Arg-1 protein expression in normal tissues of mice was gradually increased in colon ,chronic inflammatory tissues,adenomas,inflammatory carcinoma,with sta-tistical significances(P<0.05).Arg-1 expression in para -carcinoma tissue,colitis tissues,colorectal cancer tissues was gradually increased with statistical significance (P<0.05).Conclusion Arg-1 protein is associat-ed with colorectal cancer TNM stage .Arg-1 protein may be involved in occurrence and development process of inflammation-associated colon tumor and may be a candidate of proliferated and prognostic biomarker in patients with colorectal cancer .
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Argininemia(OMIM 207 800) is an autosomal recessive inherited metabolic disease of urea cycle disorders caused by deficiency of arginase I.Arginase I(AI) is the enzyme involved in the final step of the urea cycle which catalyzes the hydrolysis of arginine to ornithine and urea.The patients untreated will undergo the slowly progressive course and spastic tetraplegia,seizures and mental retardation.Unlike other urea cycle disorders,Argininemia is not generally associated with severe hyperammonemia.It is unlikely that elevated plasma ammonia is the main neurotoxic compound in argininemia because hyperammonemia rarely occurs in this condition.These neurological complications could result from the accumulation of arginine and its metabolites.argininemia can be diagnosed by ARG gene analysis or arginase acivity assay.Early diagnosis of argininemia through newborn screening program by tandem mass spectrometry may lead to a better outcome.
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Background and purpose: Arginase-1 (Arg-1) is an enzyme involved in the urea cycle. Research has shown that changed expression of Arg-1 plays an important role in the cellular metabolism and growth. The purpose of this research was to investigate the expression of Arg-1 in hepatocellular carcinoma (HCC) and to analyze its correlation with clinicopathological features. Methods: The expression of Arg-1 protein and mRNA in 31 samples of HCC, paracancerous liver tissues and 12 samples of normal liver was detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The expression profiles of Arg-1 at protein level in 158 samples of HCC and paracancerous liver tissues were detected with high-throughput tissue microarray technique and immunohistochemistry. The relationships between Arg-1 expression and clinicopathological features were also analyzed. Results:The expression of Arg-1 mRNA and protein was signiifcantly decreased in HCC compared with the paracancerous liver tissues and normal liver tissues (F=57.83, 160.89; all P<0.01). The expression of Arg-1 in HCC was related to differentiation degree (F=10.41, 30.03; all P<0.01). And with tumor differentiation decreased, the expression level down-regulated. Immunohistochemistry revealed that Arg-1 protein was mainly located in the cytoplasm and nuclear. The expression rates of Arg-1 were 88%, 98.7%and 100%in HCC, paracancerous tissues and normal liver tissues, respectively. Statistical analysis revealed that Arg-1 protein staining rate was signiifcantly lower in tumor tissues than that in paracancerous tissues (χ2=14.7416, P<0.01) and normal liver tissues (χ2=4.1415, P<0.05). The Arg-1 expression was correlated with differentiation degree of HCC, vascular invasion and recurrence after operation (χ2=22.8459, 10.2639, 10.6368 respectively;all P<0.05), but not correlated with age, gender, the hepatitis B virus, the level of serum AFP, liver cirrhosis, diameter of tumor and tumor number. Conclusion:The expression level of Arg-1 is much lower in HCC than that in the paracancerous liver and normal liver. Moreover, Arg-1 expression level is closely related to tumor differentiation degree, metastasis and relapse. These data demonstrate that Arg-1 may play a negative role in the development of HCC.
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To better understand the role of macrophages in early stages of experimental autoimmune myocarditis (EAM), we compared the expression of inducible nitric oxide synthase (iNOS) and arginase-1, markers for classically activated M1 and alternatively activated M2 macrophages, respectively, in the hearts of EAM-affected and control rats. Immunohistochemical evidence revealed that both iNOS-positive and arginase 1-positive macrophages were found in EAM lesions, while some cells were co-localized with both markers. This finding suggests that the increased level of arginase-1, which is partly from M2 macrophages, contributes to the modulation of EAM, possibly through the reduction of nitric oxide in the lesion.