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Objective:To compare the efficacy of sakubatril valsartan and valsartan in the treatment of patients with chronic cardiac insufficiency and the influence on zinc finger protein A20 and nuclear factor-κB (NF-κB) in peripheral bloodmononuclear cells (PBMCs).Methods:Ninety-senven patients with chronic cardiac insufficiency admitted to the Affiliated Hospital of Jining Medical College from February 2019 to January 2020 were continuously selected and randomly divided into the control group (48 cases) and the observation group (49 cases). Both groups received routine anti-heart failure according to the guidelines. The control group added with valsartan and the observation group added with sakubatril valsartan treatment. Before the treatment and after 3 months of treatment, the changes of cardiac function indexes and the changes of inflammatory markers such as hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP-9), and N-terminal pro B-type natriuretic peptide (NT-proBNP) were compared. PBMCs was extracted to detect zinc finger protein A20 and NF-κB levels. The incidence of adverse reactions in the two groups was recorded, and the relationship between zinc finger proteins A20, NF-κB and the myocardial injury marker NT-proBNP were analyzed.Results:After 3 months of treatment, the changes of cardiac function indexes in the observation group were better than those in the control group and the levels of hs-CRP, TNF-α, MMP-9, NT-proBNP in the observation group were lower than those in the control group: (1.96 ± 0.57) mg/L vs. (2.87 ± 0.79) mg/L, (7.11 ± 1.46) μg/L vs. (8.24 ± 1.57) μg/L, (110.14 ± 10.63) μg/L vs. (129.52 ± 17.96) μg/L, (716.91 ± 105.78) ng/L vs. (965.25 ± 97.41) ng/L, there were statistical differences ( P<0.05). After 3 months of treatment, the levels of finger protein A20, NF-κB in the observation group were lower than those in the control group: (3.57 ± 1.13) % vs. (4.41 ± 1.32) %, (29.87 ± 6.58) ng/L vs. (35.71 ± 10.02) ng/L, there were statistical differences ( P<0.05). Finger protein A20 and NF-κB in patients with chronic cardiac insufficiency were positively correlated with NT-proBNP ( r = 0.487, 0.738, P<0.01). Conclusions:On the basis of conventional treatment, compared with valsartan, the addition of sakubatril valsartan, can improve the cardiac function of patients with chronic cardiac insufficiency, reduce the body′s inflammatory response, reduce the expression of myocardial injury marker NT-proBNP, inhibit the activation of PBMCs NF-κB, and reduce the level offinger protein A20.
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Atherosclerosis, as a chronic inflammatory disease, is the most common one among cardiovascular system disorders. Inflammation is crucial in the development of atherosclerosis, which participates in the entire process of atherosclerosis. NF-κB can target to most inflammatory factors, and excessive NF-κB activation aggravates atherosclerosis development. Previous stud- ies have shown that the zinc finger protein A20 plays a key role in the anti-inflammatory and anti-apoptotic response. Research advances on A20 in protection of atherosclerosis are thus summa-rized in this review.
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Objective To observe the expression of zinc finger protein A20(A20), NF-κB and related inflammatory factors before and after lipopolysaccharide (LPS) stimulates degeneration of rabbit intervertebral disc nucleus pulposus cells.Methods The normal and degenerative nucleus pulposus cells were isolated and cultured, then divided into normal group,degenerative group,LPS stimulation group and NF-κB inhibition group.HE staining observe the morphological changes of nucleus pulposus and annulus fibrosus,immunohistochemistry was used to detect the expression of A20,NF-κB/p65 and COL-Ⅱ.Real-time PCR was employed to analyze the expression of A20,IL-1β,TNF-α,NF-κB and COL-Ⅱ,Western blot was used to observe the A20 protein,p65 and COL-Ⅱexpression in the four groups, and TNF-α, IL-1β in cell supernatant was determined by ELISA.Results The number of nucleuspulposus cells significantly decreased, aggregation occured in the degenerative group.COL-Ⅱ was obvious lower and A20, p65 significantly higher than that in normal group by immunohistochemical staining.Compared with the normal group,A20,TNF-α,IL-1β,p65 expression was significantly increased and COL-Ⅱ decreased in the mRNA and protein levels in degenerative group.Above indexes changed more significant in LPS stimulation group than in degenerative group.The expression of A20, TNF-α, IL-1β, p65 in the NF-κB inhibitor group was lower than that in the LPS group, and the expression of type Ⅱ collagen increased(P<0.05).Conclusions Intervertebral disc inflammatory response is closely related to the development of intervertebral disc degeneration, A20 may play an important role.
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The zinc finger protein A20 exists in many kinds of ceils in the body and plays multiple roles in physiological and pathological processes such as regulation of immune response,inflammatory diseases and cancers by inhibiting cell apoptosis induced by tumor necrosis factor (TNF) and restricting NFKB signaling pathway.Recently,the role of A20 in generation and development of tumors draws wide attention,hence,we summarized recent research progress of the relation between A20 and cancer in this review.
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Objective This study aimed to investigate the effect of splenic CD11clow CD45RBhigh dendritic cell (DC)derived from endotoxin tolerance (ET)mice on the expression of zinc finger protein A20 in acute liver failure (ALF)and to clarify the possible mechanism.Methods ET mice were modeled. CD11clow CD45RBhigh DC were isolated from spleen by magnetic activated cell sorting (MACS).One hundred and twenty-six healthy male BALB/c mice were randomly divided into four groups:control group (group A,n=6),ALF group (group B,n =40),normal CD11clow CD45RBhigh DC-treated group (group C,n=40),ET-CD11clow CD45RBhigh DC-treated group (group D,n=40).Mice in group B,C and D were injected with D-galactosamine (D-GalN)600 mg/kg and lipopolysaccharides (LPS)10 μg/mouse.Mice in group A were given the same volume of normal saline (NS).Half an hour after the D-GalN/LPS injection,mice in group C were treated with splenic CD11clow CD45RBhigh DC derived from normal mice (1 ×10 6/mouse,0.2 mL/mouse).Mice in group D were treated with splenic CD11clow CD45RBhigh DC derived from ET mice (1 × 10 6/mouse,0.2 mL/mouse).Mice in group A and B were given the same volume of 0.9% NaCl solution (0.2 mL/mouse).Alanine aminotransferase (ALT)and aspartate aminotransferase (AST)levels were measured at each time point.Liver histopathological changes were confirmed by hematoxglin and eosin methods.Expressions of tumor necrosis factor-α (TNF-α),nuclear factor-kappa B (NF-κB),and zinc finger protein A20 were measured by reverse transcriptase polymerase chain reaction(RT-PCR)and Western blot.One-way analysis of variance was used to compare means between groups.Normal distribution and homogeneity of variance were tested.LSD test was conducted in patients accorded with homogeneity of variance.Results ALT and AST levels increased 2 h after modeling in group B and peaked at 24 h,which were significantly higher than groups A (t = 31 .00, 11 .52,both P <0.05).ALT and AST levels also increased after 2 h after modeling and peaked at 24 h in group C and group D,which were both significantly higher than group B (t =14.60,26.43,both P <0.05).The mRNA levels and protein expressions of TNF-αand NF-κB in group B increased gradually and peaked at 12 h after D-GalN/LPS injection.Compared to that of group A,the differences were both statistically significant (t = 427.58,122.42,179.35 ,165 .98,all P < 0.05 ).The mRNA level and protein expression of zinc finger protein A20 in group B decreased gradually and reached the minimum at 12 h after D-GalN/LPS injection,which was statistically different compared to group A (t = 90.80, 160.43,both P <0.05).On the contrary,the levels of zinc finger protein A20 in group C and D increased gradually and peaked at 12 h after D-GalN/LPS injection.The expression level of zinc finger protein A20 in group D was significantly higher than group C (t = 11 .21 ,24.80,both P < 0.05 ).Conclusion Treatment of splenic CD11clow CD45RBhigh DC derived from ET mice contributes to liver protection against D-GalN/LPS-induced ALF.
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Objective To investigate the effects of the zinc finger protein A20 on LPS-TLR4 signaling pathways in severe acute pancreatitis(SAP) rats.Methods 24 SD rats were randomly divided into 3 groups:group A(the sham operation group),group B (the SAP group),group C (the SAP group treated with LPS).SAP model was induced by retro-injection of intraductal 5％ sodium taurocholate into the biliary-pancreatic duct as previously described.The protein expression of A20,TLR4,NF-κBp65 and p38MAPK in pancreatic tissues was evaluated by immunohistochemistry.Results The positive area of A20 in pancreatic tissues was decreased in group B and group C compared with that in group A (t =17.234,19.698,all P ＜ 0.05).On the contrary,the expression of TLR4,NF-κBp65 and p38MAPK in pancreatic tissues were up-regulated(t =15.909,20.432,16.543,18.629,22.105,19.006,all P ＜ 0.05).A20 was decreased in group C than that in group B (t =14.894,P ＜ 0.05),while TLR4、NF-κBp65 and p38MAPK were increased in group C than those in group B (t =14.047,15.582,17.070,all P ＜0.05).Conclusion The expression of A20 reduced and TLR4,NF-κBp65 and p38MAPK enhanced in the pancreas of rats with SAP,which indicated that A20 inhibited LPS-TLR4 signaling pathways which play important roles in the pathogenesis of SAP.
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Objective To measure the expressions of zinc finger protein A20 and nuclear factor (NF)-κB in cutaneous squamous cell carcinoma (CSCC) tissue and their correlation with human papillomavirus (HPV) infection.Methods Tissue specimens were obtained from the lesions of 43 patients with CSCC and normal skin of 21 healthy human controls.Gene chips were used to detect the DNA of 21 HPV subtypes in these specimens.The expression levels of zinc finger protein A20 and NF-κB were determined by immunohistochemistry.The correlation between clinicopathological features of CSCC and HPV infection was estimated by Spearman rank correlation analysis.Results No significant difference was found in the expression level of either zinc finger protein A20 or NF-κB among patients of different age groups,gender,and with CSCC of different primary sites or histological grade (all P ＞ 0.05).However,there was a significant difference in the expression levels of zinc finger protein A20 and NF-κB between 39 patients with histological grade Ⅰ or Ⅱ and 4 patients with grade Ⅲ (25.85 ± 3.84 vs.48.34± 7.69 for zinc finger protein A20,46.64 ± 8.93 vs.57.34 ± 10.02 for NF-κB,both P ＜ 0.05),and between 3 patients with nodular metastasis and 40 patients without (35.34 ± 6.02 vs.26.51 ± 4.09 for zinc finger protein A20,57.53 ± 13.32 vs.45.45 ± 9.64 for NF-κB,P ＜ 0.05 or 0.01).The expression rate was 2/8,5/13 and 1/3 for zinc finger protein A20 (P ＞ 0.05),3/8,10/13 and 2/3 for NF-κB (P ＞ 0.05),in CSCC tissue specimens infected with low-risk HPV subtypes,high-risk subtypes,concurrent low-and high-risk HPV subtypes respectively.In HPV-infected CSCC tissue,a significantly positive correlation was found between the staining scores for zinc finger protein A20 and for NF-κB p65(r =3.14,P ＜ 0.05).Conclusion The high expressions of NF-κB and zinc finger protein A20 may play an important role in the oncogenesis of CSCC induced by HPV infection.
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Objective To explore the effects of zinc finger protein A20(A20) on the expression of CD40 and the phosphorylation of IκBαas well as the local inflammatory reaction of abdominal cavity in Sprague Dawley (SD) rats with peritoneal dialysis-related a-cute peritonitis induced by lipopolysaccharide (LPS ) .Methods 24 male SD rats were equally randomized to four groups (n= 6 , each) .Control group:injected with 4 .25% dextrose peritoneal dialysate(PDF) via abdominal cavity (90 mL/kg);LPS group :injec-ted with LPS(1 mg/kg) via abdominal cavity 4 hour later followed by PDF injection ;transfection A20 plasmid group and empty plasmid group:after transfer pGEM-T easy-A20 or pGEM-T easy plasmid via intraperitoneally using an ultrasound-microbubble-mediated system for 3 days ,then injected with LPS and PDF via abdominal cavity .The rats were killed 4 hours after PDF injection . Peritoneum tissue was stained using Masson and HE .Leucocytes count in abdominal dropsy was performed .The proteins expres-sion of A20 ,p-IκBα,IκBα,and CD40 in peritoneum tissue were analyzed by western blot ;the expression of CD40 mRNA in peritone-um tissue were determined by RT-PCR;IL-6 level in abdominal dropsy was determined by ELISA .Results LPS could induce the protein expression of A20 in rats peritoneum tissue .Compared with LPS group and empty plasmid group ,the degree of edema ,in-flammatory cells infiltration ,and the ratio of p-IκBα/IκBα,mRNA and protein expression of CD40 in rats peritoneum as well as leu-cocyte counts and IL-6 level of abdominal dropsy were also significantly decreased in transfection A20 plasmid group(P0 .05) ,but the mRNA and protein expression of CD40 were significantly higher than that of control group (P<0 .05) .Conclusion Over expression of A20 in SD rats peritoneum tissue could down-regulate the inflammatory reaction in peritonitis induced by LPS ,which might be involved in modulating the expression of associated functional protein during LPS signal pathw ay .
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Objective To investigate the protein and mRNA expression of NF-κB and zinc finger protein A20 in the keloid and normal skin and to explore its underlying molecular biological mechanism.Methods The protein and mRNA expression of NF-κB p65 and zinc finger protein A20 in keloid and normal skin was detected by immunohistochemistry and real time quantitative reverse transcription-polymerase chain reaction (RT-PCR).Results The protein and mRNA expression of NF-κB p65 in keloid tissues was higher than those in normal skin tissues (P＜0.05).The protein and mRNA expression of zinc finger protein A20 in keloid tissues was lower than those in normal skin tissues (P＜0.05).Conclusions NF-κB signal pathways and zinc finger protein A20 could play a role in keloid pathogenesis.
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As a zinc finger protein with ubiquitin-modifying activity, A20 is highly expressed in most mammalian cell in response to stimuli of tumor necrosis factor (TNF), lnterleukin-1 (IL-1), lipopolysaccharide (LPS) and other factors. A20 has been found to play a crucial effect in control of the cell maturation, cytokine production and immunostimulatory potency of dendritic cells (DCs) via modulating down-regulation of NF-κB signaling transduction pathway. In this brief review, we descript the biological characteristics of A20 and the involvement of the A20 in the pathway of the immune responses toward to the DC cell maturation and immunostimulatory potency.
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Objective To study the expression law of zinc finger protein A20 mRNA of mouse liver tissues in the process of trauma with lipopolysaccharide (LPS) infection. Methods A total of 95 healthy mice (either sex, from Kunming, Yunnan province) with a mean body weight of 21 g (18-24 g) were randomized into 4 groups: control, trauma only (Group A), LPS only (Group B) and trauma plus LPS (Group C). The models with closed fracture of bilateral spines as well as endotoximia were made. The expression characteristics of zinc finger protein A20 mRNA of liver tissues were measured by reverse transcription-polymerase chain reaction (RT-PCR) and all result data expressed as total gray ratio of A20 mRNA to GAPDH mRNA (?s). Results In the control group, the A20 mRNA expressed at a low level. There was low expression of zinc finger protein A20 in the Group A at various time points, with no significant difference compared with the control group. After LPS infection, the expression of A20 mRNA in the Group B was elevated more obviously than that in the control group at 0.5 hour, reached peak during 0.5-2 hours and decreased after 2 hours. But expression of A20 mRNA at each time point was higher in the Group B than that in the Group A. In the Group C, after LPS infection, the expression of A20 mRNA was elevated more significantly than that in other two groups 0.5 hour, reached the highest level during 0.5-2 hours, much higher than that in the Group B (P
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Objective To investigate the effect of zinc finger protein A20 expression on lipopolysaccharide(LPS)response in human monocytes so as to discuss its regulation roles and mechanism to inflammation in vivo and its potential value of clinical application.Methods Cell transfection technique was respectively used to make zinc finger protein A20 transgenic cell model and gene silence cell model,both of which were then treated with LPS.Real-time reverse PCR was employed to analyze the expression of zinc finger protein A20 and ELISA to determine the activity of nuclear transcription factor NF-?B and the levels of dependent inflammatory cytokines including tumor necrosis factor(TNF)alpha.Results After LPS treatment,the NF-?B activity and the TNF-alpha level were significantly lower in the cells with overexpressed zinc finger protein A20 than LPS control cells(P