Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneou...Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.展开更多
Background： Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1 （ESR 1）. The polymorp...Background： Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1 （ESR 1）. The polymorphisms ofESR 1 were involved in recurrent spontaneous abortion （RSA）; however, the association between ESRI polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESRI Pvull （-397C/T, rs2234693） and Xbal （-351 A/G, rs9340799） polymorphisms and the risk of RSA. Methods： All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3,2018. Data were processed in the Stata 12.0 software. The odds ratios （ORs） and 95% confidence intervals （95% Cls） were calculated using fixed-effects models （FEM）/random-effects models （REM）. Results： Seven case-control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR 1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model （OR = 2.40, 95% CI = 1.05-5.50, P = 0.039）. Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model （OR = 0.53, 95% CI = 0.33-0.85, P = 0.009） and the dominant genetic model （OR=0.55, 95% CI = 0.30 0.98, P = 0.042）. Conclusions： Generally. there was no significant association between the polymorphisms of ESRI and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.展开更多
Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitme...Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4^＋ T cells. Methods Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 （SA group, n=14）, the normal pregnant mouse model CBA/JxBALB/c （NP group, n=13）, and normal non-pregnant CBA/J mice （NNP group, n=11）. The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4^＋ T cells was measured by double-label flow cytometry （FCM） method. Results In peripheral blood, the SA group had significantly lower CCR3 expression （P 〈0.01） and higher CCR5 and CXCR3 expression （P 〈0.01） on CD4^＋ T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference （P 〉0.05）. In spleen, the SA group expressed significantly lower CCR3 expression （P 〈0.01） and higher CCR5 and CXCR3 expression （P 〈0.05） on CD4^＋ T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression （P 〈0.01）, but was not statistically different with regards to the other two chemokines （P 〉0.05）. In thymus, the SA group had significantly lower CCR3 expression （P 〈0.05） and higher CXCR3 expression （P 〈0.05） on CD4^＋ T cells than the NP group, with no significant difference in CCR5 expression （P 〉0.05）. Compared with the NNP group, the SA group had higher CCR3 expression （P 〈0.01）, but there was no statistical difference in CXCR3 and CCR5 expression （P 〉0.05） between the two groups. Conclusion The abnormal expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells may play an important role in the pathogenesis of spontaneous abortion.展开更多
Background Experimental evidence indicates that cyclooxygenase-2 （COX-2） plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion ...Background Experimental evidence indicates that cyclooxygenase-2 （COX-2） plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion （URSA）. Methods We evaluated the expression level and potential signaling pathway of COX-2 in 30 cases of URSA who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious, autoimmune diseases and in 30 normal pregnancies. Results The mRNA and the protein expression level of COX-2 in the URSA group （-0.238±0.848, 0.368±0.089, respectively） were significantly lower than that in the control group （1.943±3.845, 1.046±0.108, respectively） （both, P 〈0.01）. The expression of prostaglandins PGF2a, PGD2, PGE2, and PGI2, in the URSA group （（2326.0±295.6） pg/ml, （2164.0±240.5） pg/ml, （238.7±26.4） pg/ml, （2337.0±263.0） pg/ml, respectively） were significantly lower than that in the control group （（3450.0±421.7） pg/ml, （3174.0±415.6） pg/ml, （323.5±43.8） pg/ml, （3623.0±460.4） pg/ml, respectively） （P 〈0.05）. The mRNA expression level of PPARI3 and RXRa （0.859±0.653, -0.172±0.752, respectively） in URSA group was significantly lower than that in the control group （1.554±1.735, 0.777±2.482, respectively） （both P 〈0.05）. The mRNA and protein expression levels of vascular endothelial growth factor-A （VEGF-A） in the URSA group （2.010±1.522, 0.35±0.46） was significantly lower than that in the control group （4.569±2.430, 0.750±0.350） （both P 〈0.05）. Conclusions COX-2 and the COX-2-derived PGI2 signaling pathway possibly play an important role in successful embryo implantation, and their decreased expression may result in URSA. The decreased expression may influence the expression of VEGF-A which interferes with placental angiogenesis causing failure of embryo implantation, leading to spontaneous abortion.展开更多
Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, ...Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase(SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.展开更多
Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pa...Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors （PPARs） have been identified： PPARa, PPARβ/δ, and PPARγ, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats （SHR） and to understand the modulation of endogenous PPAR isoforms under inflammatory condition. Methods l]ssues （kidney, liver, heart, and brain） were dissected from SHR and age-matched control Wistar-Kyoto rats （WKY） to investigate the abundance of PPAR isoforms and PPAR-responsive genes （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase （iNOS）, intercellular adhesion molecule-1 （ICAM-1）, vascular cell adhesion molecule-1 （VCAM-1）, E-selectin, interleukin-1 beta （IL-1β）, and tumor necrosis factor alpha （TNFα）, and formation of carbonyl and nitrated proteins. Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR. Conclusions These findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes （increases） in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.展开更多
Hepatocellular carcinoma （HCC） is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation betwe...Hepatocellular carcinoma （HCC） is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus （HBV） infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer （NK） cells express a large number of immune recognition receptors （NK receptors （NKRs）） to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono- and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC.展开更多
文摘Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.
基金This work was supported by the Natural Science Foundation of China （No. 81373670, No. 81673981, and No. 81601442）, the Primary Research and Development Plan of Shandong Province （No. 2016GSF202016, No. 2017GSF19118, 2017G006018, and No. 2017GSF218013）, the Project of Transformation in High-tech Achievements （No. 2013ZHZX2A0405）, the Science and Technology Development Grant of the State Administration of traditional Chinese medicine of Shandong Province （No. 2013-2016 and No. 2017-174）, the Family Planning Committee of Shandong Province （No. [2014] 14）, the Project for Shandong Medical and Health Science and Technology Plan （No. 2015WS0191）, the Project of Science and Technology of Shandong Academy of Medical Sciences （No. 2016-34, No. 2016-35, and No. 2017-15）, and the Innovation Project of Shandong Academy of Medical Sciences.
文摘Background： Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1 （ESR 1）. The polymorphisms ofESR 1 were involved in recurrent spontaneous abortion （RSA）; however, the association between ESRI polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESRI Pvull （-397C/T, rs2234693） and Xbal （-351 A/G, rs9340799） polymorphisms and the risk of RSA. Methods： All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3,2018. Data were processed in the Stata 12.0 software. The odds ratios （ORs） and 95% confidence intervals （95% Cls） were calculated using fixed-effects models （FEM）/random-effects models （REM）. Results： Seven case-control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR 1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model （OR = 2.40, 95% CI = 1.05-5.50, P = 0.039）. Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model （OR = 0.53, 95% CI = 0.33-0.85, P = 0.009） and the dominant genetic model （OR=0.55, 95% CI = 0.30 0.98, P = 0.042）. Conclusions： Generally. there was no significant association between the polymorphisms of ESRI and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.
基金This study was supported by a grant from the Natural Science Foundation of Shanghai （No.07ZR14072）.We are grateful to Yael Saden Barach （Albert Einstein College of Medicine, New York） for editing this manuscript.
文摘Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4^＋ T cells. Methods Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 （SA group, n=14）, the normal pregnant mouse model CBA/JxBALB/c （NP group, n=13）, and normal non-pregnant CBA/J mice （NNP group, n=11）. The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4^＋ T cells was measured by double-label flow cytometry （FCM） method. Results In peripheral blood, the SA group had significantly lower CCR3 expression （P 〈0.01） and higher CCR5 and CXCR3 expression （P 〈0.01） on CD4^＋ T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference （P 〉0.05）. In spleen, the SA group expressed significantly lower CCR3 expression （P 〈0.01） and higher CCR5 and CXCR3 expression （P 〈0.05） on CD4^＋ T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression （P 〈0.01）, but was not statistically different with regards to the other two chemokines （P 〉0.05）. In thymus, the SA group had significantly lower CCR3 expression （P 〈0.05） and higher CXCR3 expression （P 〈0.05） on CD4^＋ T cells than the NP group, with no significant difference in CCR5 expression （P 〉0.05）. Compared with the NNP group, the SA group had higher CCR3 expression （P 〈0.01）, but there was no statistical difference in CXCR3 and CCR5 expression （P 〉0.05） between the two groups. Conclusion The abnormal expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells may play an important role in the pathogenesis of spontaneous abortion.
文摘Background Experimental evidence indicates that cyclooxygenase-2 （COX-2） plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion （URSA）. Methods We evaluated the expression level and potential signaling pathway of COX-2 in 30 cases of URSA who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious, autoimmune diseases and in 30 normal pregnancies. Results The mRNA and the protein expression level of COX-2 in the URSA group （-0.238±0.848, 0.368±0.089, respectively） were significantly lower than that in the control group （1.943±3.845, 1.046±0.108, respectively） （both, P 〈0.01）. The expression of prostaglandins PGF2a, PGD2, PGE2, and PGI2, in the URSA group （（2326.0±295.6） pg/ml, （2164.0±240.5） pg/ml, （238.7±26.4） pg/ml, （2337.0±263.0） pg/ml, respectively） were significantly lower than that in the control group （（3450.0±421.7） pg/ml, （3174.0±415.6） pg/ml, （323.5±43.8） pg/ml, （3623.0±460.4） pg/ml, respectively） （P 〈0.05）. The mRNA expression level of PPARI3 and RXRa （0.859±0.653, -0.172±0.752, respectively） in URSA group was significantly lower than that in the control group （1.554±1.735, 0.777±2.482, respectively） （both P 〈0.05）. The mRNA and protein expression levels of vascular endothelial growth factor-A （VEGF-A） in the URSA group （2.010±1.522, 0.35±0.46） was significantly lower than that in the control group （4.569±2.430, 0.750±0.350） （both P 〈0.05）. Conclusions COX-2 and the COX-2-derived PGI2 signaling pathway possibly play an important role in successful embryo implantation, and their decreased expression may result in URSA. The decreased expression may influence the expression of VEGF-A which interferes with placental angiogenesis causing failure of embryo implantation, leading to spontaneous abortion.
基金supported b y the Na tional In stitu te o f Health(1R01CA172268)the Leukemia&Lymphoma Society(1024-14+7 种基金TRP-6024-14)the Robert A.Welch Foundation(I-1834)the Cancer Prevention and Research Institute of Texas(RP140402 and DP150056)the Innovation Program of Shanghai Municipal Education Commission(13G20)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learningthe National Natural Science Foundation of China(813706548142200181471524)
文摘Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase(SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.
基金This work was supported by grants from E-Institutes for Nitric Oxide and Inflammatory Medicine of Shanghai Universities （No. E-04010） Key Project of Shanghai Committee of Science ＆ Technology （No. 05JC14056）+1 种基金 Key Project of Shanghai Municipal Education Commission （No. 05ZZ11） National Natural Science Foundation of China （No. 30500169）.
文摘Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors （PPARs） have been identified： PPARa, PPARβ/δ, and PPARγ, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats （SHR） and to understand the modulation of endogenous PPAR isoforms under inflammatory condition. Methods l]ssues （kidney, liver, heart, and brain） were dissected from SHR and age-matched control Wistar-Kyoto rats （WKY） to investigate the abundance of PPAR isoforms and PPAR-responsive genes （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase （iNOS）, intercellular adhesion molecule-1 （ICAM-1）, vascular cell adhesion molecule-1 （VCAM-1）, E-selectin, interleukin-1 beta （IL-1β）, and tumor necrosis factor alpha （TNFα）, and formation of carbonyl and nitrated proteins. Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR. Conclusions These findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes （increases） in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.
基金This work was supported by grants from the Chinese Government Department of Science ＆ Technology of China （2012ZX10002006 2012ZX 10002014+4 种基金 2013 ZX 10002002 2012AA020901 2010CB911901 2013CB944901） and the Natural Science Foundation of China （81273220 81472646）.
文摘Hepatocellular carcinoma （HCC） is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus （HBV） infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer （NK） cells express a large number of immune recognition receptors （NK receptors （NKRs）） to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono- and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC.
