Separate regression models were also tested with the individual c

Separate regression models were also tested with the individual components of MS (considered as continuous or categorical measures) simultaneously included in the same equation. We took the maximum value of cIMT as the dependent variable in the regression models because the strongest association between the different measurements of IMT and coronary risk factors in otherwise healthy individuals

is achieved by applying the maximum value of IMT and not the mean value of IMT.17 A P value of less than check details 0.05 was considered statistically significant. A total of 250 obese children and adolescents, 100 with ultrasound-diagnosed NAFLD (and elevated ALT) and 150 without liver involvement, as well as 150 healthy normal-weight subjects were included in the study analysis (Fig. 1). None of the 250 obese children had type 2 diabetes mellitus. Baseline clinical and laboratory characteristics of the study population are presented in Table 1. MS, as well as MS components, were significantly more prevalent in obese children with NAFLD than in those without NAFLD (Table 2). At baseline, no differences were observed in the diameter of the brachial artery among the study groups (Table 1). In response to ischemia, obese children with NAFLD had significantly reduced

FMD compared to those without NAFLD and CP-690550 in vitro to healthy controls. In addition, percent FMD was remarkably larger in obese children without MS compared to obese children with MS (12.8% [95% CI, 11.0 to 14.5] versus 7.78% [5.30 to 10.2]; P < 0.01). When subdividing the obese population into subjects with and without MS, and with and without NAFLD, the FMD response was lower in children with MS and NAFLD than in those without MS and NAFLD (Fig. 2A). In

the entire study population, low percent FMD was significantly associated selleck with BMI-SDS, WC, high arterial BP, high triglycerides, high glucose, IR, CRPHS levels, and low HDL cholesterol after adjustment for age, gender, and Tanner stage (Table 3). Moreover, low percent FMD was associated with MS and NAFLD (Table 3). When the obese group was analyzed separately, low percent FMD was significantly associated with BMI-SDS, WC, high glucose, IR, CRPHS levels, and low HDL cholesterol, as well as with MS and NAFLD (Table 3). None of the variables were associated with FMD in the healthy group after correction for age, gender, and Tanner stage. When multiple logistic regression analysis was performed after adjusting for age, gender, Tanner stage, and MS (considered as a single clinical entity), NAFLD was significantly associated with low percent FMD (Table 4). Even after adjustment for age, gender, Tanner stage, and the individual components of MS, NAFLD remained significantly associated with low percent FMD. In this model, other covariates independently associated with low percent FMD were high glucose or IR (Table 4). Similar results were found when we considered FMD as a continuous measure and performed multivariate linear regression analyses.

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(2010), we found a strong correlation between past and future int

(2010), we found a strong correlation between past and future internal details (r = .63, p < .01) and past and future external details (r = .73, p < .001). In contrast, past internal and external details were uncorrelated (r = .30, p = .23) as were future internal and external details (r = .06, p = .82). The positive correlations between internal and external

details for past and future events AZD4547 nmr have been accounted for as evidence for the close overlap between the specificity of past and future events (Addis et al., 2008). However, it should be kept in mind that these correlations are boosted by the large differences between the TBI and control group, and therefore should be interpreted with caution. To take into account the fact that patients produced fewer details overall and to examine the effect of temporal distance to the remembered/imagined event together with the other factors, we looked at the ratio of internal-to-total details. The ratios were

analysed by means of a 2 (Group: TBI vs. controls) × 2 (Temporal Direction: past vs. future) × 3 (Temporal Distance: 1 month, 5 years, or 10 years) mixed-factor analyses of variance (ANOVA) with Group as a between-subject factor, and Temporal Direction and Temporal Distance as within-subjects factors. As illustrated by Figure 2, a significant main effect of Group was found, F(1, 16) = 58.18, η2p = .78, p < .0001, together with a significant Epacadostat effect of Temporal Direction, F(1, 16) = 15.34, η2p = .49, p < .001, and Temporal Distance F(1, 16) = 12.18, η2p = .43, p < .0001.

The main effect of Group reflected, that the TBI participants proportionally reported fewer episodic event-specific details for both past and future events compared with healthy controls across all time periods. The main effect of Temporal Direction indicated that proportionally more episodic event-specific details were produced for past events than for future events. The main effect of Temporal Distance reflected that events closer in time contained a greater proportion of episodic event-specific details than distant events. Importantly, the Temporal Distance × Group interaction was significant. The results of a repeated measures ANOVA performed on each group separately showed that the Temporal Distance effect was significant only for the TBI participants, F(2, 16) = 10.66, η2p = .57, find more p < .001, but not for the controls F(2, 16) = 2.00, p = .17, reflecting that TBI patients produced proportionally fewer episodic, event-specific details for past and future events the further the events were located away from the present. In sum, this series of analyses showed that TBI patients’ representations contained relatively fewer episodic, event-specific details than the ones of the controls, even when controlling for the total number of details. Moreover, while the TBI patients reported proportionally fewer internal details than did the healthy controls, this trend was not symmetrical.

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Although the miRNA family constitutes only a minor fraction of th

Although the miRNA family constitutes only a minor fraction of the human

genome, they hold fundamental importance in diverse physiological and developmental processes due to their pleiotropic effects on the post-transcriptional regulation of many vital genes. This class of regulatory RNAs has also emerged as important players in carcinogenesis; most, if not all, cancer types have abnormal miRNA expression patterns. In hepatocellular carcinoma (HCC), miRNA dysregulation plays a key role in mediating the pathogenicity of several etiologic risk factors and, more importantly, they promote a number of cancer-inducing signaling pathways. Recent studies have also demonstrated their potential values in the clinical management of HCC patients as some miRNAs may be used as prognostic GSK-3 inhibitor or diagnostic markers. The significance of miRNAs in liver carcinogenesis emphasizes their values as therapeutic targets, while technological advances in the delivery of miRNA has shed new possibilities for their use as novel therapeutic agents against HCC. In the past few decades, genome

research has established the fundamental importance of genetic and epigenetic alterations of oncogenes and tumor suppressor genes (TSGs) in the initiation and progression of human neoplasms. The recent discovery of microRNA (miRNA) put forward an alternate regulatory element, in which the check details actions of miRNAs regulate cancer-inducing cellular genes post-transcriptionally. The founding member of miRNA, lin-4, was discovered in the larval development of Caenorhabditis selleck elegans in 1993.1 Nevertheless, the role of small RNA in gene expression regulation had to await the discovery of a second miRNA member, let-7, 7 years later.2 Pioneering studies further revealed let-7 as a negative regulator of the RAS oncogene in human tumor cells.3 This discovery soon aroused tremendous efforts into the research of cancer-related miRNAs. By now,

miRNAs have been reported in a variety of organisms, ranging from viruses to mammals. To facilitate miRNA research, a miRNA registry (miRBase) has been established and is currently maintained by the University of Manchester.4 So far, 940 human miRNAs have been reported (miRBase release 15) and the list is still expanding. The family of miRNA constitutes about 1–3% of the human genome. Most miRNA genes are situated within the intergenic regions and have their own transcription units. About a quarter are located within exons or introns of other coding genes where their transcription is controlled by the host genes. MiRNAs can be transcribed as monocistronic transcripts or in polycistronic clusters; the latter involves several miRNAs situated on a single transcript being controlled by the same promoter (Fig. 1). In the nucleus, miRNA genes are transcribed as primary-miRNAs (pri-miRNAs) by RNA polymerase II (PolII).

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Although the miRNA family constitutes only a minor fraction of th

Although the miRNA family constitutes only a minor fraction of the human

genome, they hold fundamental importance in diverse physiological and developmental processes due to their pleiotropic effects on the post-transcriptional regulation of many vital genes. This class of regulatory RNAs has also emerged as important players in carcinogenesis; most, if not all, cancer types have abnormal miRNA expression patterns. In hepatocellular carcinoma (HCC), miRNA dysregulation plays a key role in mediating the pathogenicity of several etiologic risk factors and, more importantly, they promote a number of cancer-inducing signaling pathways. Recent studies have also demonstrated their potential values in the clinical management of HCC patients as some miRNAs may be used as prognostic selleck chemicals or diagnostic markers. The significance of miRNAs in liver carcinogenesis emphasizes their values as therapeutic targets, while technological advances in the delivery of miRNA has shed new possibilities for their use as novel therapeutic agents against HCC. In the past few decades, genome

research has established the fundamental importance of genetic and epigenetic alterations of oncogenes and tumor suppressor genes (TSGs) in the initiation and progression of human neoplasms. The recent discovery of microRNA (miRNA) put forward an alternate regulatory element, in which the www.selleckchem.com/products/FK-506-(Tacrolimus).html actions of miRNAs regulate cancer-inducing cellular genes post-transcriptionally. The founding member of miRNA, lin-4, was discovered in the larval development of Caenorhabditis this website elegans in 1993.1 Nevertheless, the role of small RNA in gene expression regulation had to await the discovery of a second miRNA member, let-7, 7 years later.2 Pioneering studies further revealed let-7 as a negative regulator of the RAS oncogene in human tumor cells.3 This discovery soon aroused tremendous efforts into the research of cancer-related miRNAs. By now,

miRNAs have been reported in a variety of organisms, ranging from viruses to mammals. To facilitate miRNA research, a miRNA registry (miRBase) has been established and is currently maintained by the University of Manchester.4 So far, 940 human miRNAs have been reported (miRBase release 15) and the list is still expanding. The family of miRNA constitutes about 1–3% of the human genome. Most miRNA genes are situated within the intergenic regions and have their own transcription units. About a quarter are located within exons or introns of other coding genes where their transcription is controlled by the host genes. MiRNAs can be transcribed as monocistronic transcripts or in polycistronic clusters; the latter involves several miRNAs situated on a single transcript being controlled by the same promoter (Fig. 1). In the nucleus, miRNA genes are transcribed as primary-miRNAs (pri-miRNAs) by RNA polymerase II (PolII).

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Moreover, N2 fixation by cyanobacteria

Moreover, N2 fixation by cyanobacteria PARP inhibitor is much more likely in freshwater ecosystems than in marine ecosystems (Conley et al. 2009; but Elser et al. 2007). These findings mentioned above may lead to a more often P-deficient than N-deficient

condition and thus a good correlation between PUFAs and POP for primary producers in a lake. The correlation between FAs and QN shows that elemental and biochemical properties of phytoplankton covaried in the three species under N deficiency in our study. The incorporation of two properties is important for studying the limitation of food quality on zooplankton via bottom-up processes. On the other hand, the lack of common correlation between FAs and QP in this study might

be evidence of dominant nonphosphorus lipids in response to P deficiency in some species of marine phytoplankton. Although these two aspects are out of the scope of this study, our results can be very useful for further research on lipid biosynthetic mechanisms, as well as the energy and matter transfer in food webs. In this study, the effects of N:P supply ratios and growth rates on phytoplankton FA composition were studied in laboratory conditions. This approach this website focuses on the evaluation of these two factors in regulating biochemical quality of phytoplankton. However, phytoplankton in natural conditions faces interactive effects of multiple abiotic factors and resources, e.g., temperature, light, nutrient supply, and CO2. For example, light supply is identified as a dominant trigger of the phytoplankton spring bloom, and nutrients is suggested to define the carrying capacity of phytoplankton in the plankton ecology group model (Sommer et al. 2012). Recent studies have simultaneously considered the effects of nutrient

supply and other abiotic factors (or resources) on phytoplankton FA (or lipid) composition, e.g., the combined effect of nutrient supply and temperature (e.g., Piepho et al. 2012, Roleda et al. 2013), light intensity (e.g., Piepho et al. 2012), light:dark cycles (e.g., Lacour et al. 2012), check details or CO2 (e.g., Spijkerman and Wacker 2011). Thus, other ambient factors may influence the effects of N:P supply ratios and growth rates on phytoplankton FA composition, on which further studies are recommended for better understanding responses of chemical composition of phytoplankton in more realistic scenarios. This study examined the influence of highly variable chemical conditions (N:P supply ratios) and biological conditions (growth rates) on biochemical outcome (FA composition) in three species of marine phytoplankton (representing particular algal classes). It scaled intraspecific variation in FA profiles (simultaneously affected by nutrient supply and growth rates) against variation between phytoplankton classes, and thus provides important empirical data for further studies on phytoplankton lipid biosynthesis in changing oceans.

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Moreover, N2 fixation by cyanobacteria

Moreover, N2 fixation by cyanobacteria www.selleckchem.com/products/CP-690550.html is much more likely in freshwater ecosystems than in marine ecosystems (Conley et al. 2009; but Elser et al. 2007). These findings mentioned above may lead to a more often P-deficient than N-deficient

condition and thus a good correlation between PUFAs and POP for primary producers in a lake. The correlation between FAs and QN shows that elemental and biochemical properties of phytoplankton covaried in the three species under N deficiency in our study. The incorporation of two properties is important for studying the limitation of food quality on zooplankton via bottom-up processes. On the other hand, the lack of common correlation between FAs and QP in this study might

be evidence of dominant nonphosphorus lipids in response to P deficiency in some species of marine phytoplankton. Although these two aspects are out of the scope of this study, our results can be very useful for further research on lipid biosynthetic mechanisms, as well as the energy and matter transfer in food webs. In this study, the effects of N:P supply ratios and growth rates on phytoplankton FA composition were studied in laboratory conditions. This approach Buparlisib focuses on the evaluation of these two factors in regulating biochemical quality of phytoplankton. However, phytoplankton in natural conditions faces interactive effects of multiple abiotic factors and resources, e.g., temperature, light, nutrient supply, and CO2. For example, light supply is identified as a dominant trigger of the phytoplankton spring bloom, and nutrients is suggested to define the carrying capacity of phytoplankton in the plankton ecology group model (Sommer et al. 2012). Recent studies have simultaneously considered the effects of nutrient

supply and other abiotic factors (or resources) on phytoplankton FA (or lipid) composition, e.g., the combined effect of nutrient supply and temperature (e.g., Piepho et al. 2012, Roleda et al. 2013), light intensity (e.g., Piepho et al. 2012), light:dark cycles (e.g., Lacour et al. 2012), selleck kinase inhibitor or CO2 (e.g., Spijkerman and Wacker 2011). Thus, other ambient factors may influence the effects of N:P supply ratios and growth rates on phytoplankton FA composition, on which further studies are recommended for better understanding responses of chemical composition of phytoplankton in more realistic scenarios. This study examined the influence of highly variable chemical conditions (N:P supply ratios) and biological conditions (growth rates) on biochemical outcome (FA composition) in three species of marine phytoplankton (representing particular algal classes). It scaled intraspecific variation in FA profiles (simultaneously affected by nutrient supply and growth rates) against variation between phytoplankton classes, and thus provides important empirical data for further studies on phytoplankton lipid biosynthesis in changing oceans.

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Moreover, N2 fixation by cyanobacteria

Moreover, N2 fixation by cyanobacteria Maraviroc manufacturer is much more likely in freshwater ecosystems than in marine ecosystems (Conley et al. 2009; but Elser et al. 2007). These findings mentioned above may lead to a more often P-deficient than N-deficient

condition and thus a good correlation between PUFAs and POP for primary producers in a lake. The correlation between FAs and QN shows that elemental and biochemical properties of phytoplankton covaried in the three species under N deficiency in our study. The incorporation of two properties is important for studying the limitation of food quality on zooplankton via bottom-up processes. On the other hand, the lack of common correlation between FAs and QP in this study might

be evidence of dominant nonphosphorus lipids in response to P deficiency in some species of marine phytoplankton. Although these two aspects are out of the scope of this study, our results can be very useful for further research on lipid biosynthetic mechanisms, as well as the energy and matter transfer in food webs. In this study, the effects of N:P supply ratios and growth rates on phytoplankton FA composition were studied in laboratory conditions. This approach Ceritinib molecular weight focuses on the evaluation of these two factors in regulating biochemical quality of phytoplankton. However, phytoplankton in natural conditions faces interactive effects of multiple abiotic factors and resources, e.g., temperature, light, nutrient supply, and CO2. For example, light supply is identified as a dominant trigger of the phytoplankton spring bloom, and nutrients is suggested to define the carrying capacity of phytoplankton in the plankton ecology group model (Sommer et al. 2012). Recent studies have simultaneously considered the effects of nutrient

supply and other abiotic factors (or resources) on phytoplankton FA (or lipid) composition, e.g., the combined effect of nutrient supply and temperature (e.g., Piepho et al. 2012, Roleda et al. 2013), light intensity (e.g., Piepho et al. 2012), light:dark cycles (e.g., Lacour et al. 2012), learn more or CO2 (e.g., Spijkerman and Wacker 2011). Thus, other ambient factors may influence the effects of N:P supply ratios and growth rates on phytoplankton FA composition, on which further studies are recommended for better understanding responses of chemical composition of phytoplankton in more realistic scenarios. This study examined the influence of highly variable chemical conditions (N:P supply ratios) and biological conditions (growth rates) on biochemical outcome (FA composition) in three species of marine phytoplankton (representing particular algal classes). It scaled intraspecific variation in FA profiles (simultaneously affected by nutrient supply and growth rates) against variation between phytoplankton classes, and thus provides important empirical data for further studies on phytoplankton lipid biosynthesis in changing oceans.

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[1] In acute liver failure, the net effect of all hemostatic chan

[1] In acute liver failure, the net effect of all hemostatic changes is not clear, partly because the changes in the hemostatic system in these patients have been less well defined compared with those in patients with cirrhosis. In an effort to elucidate this issue, we are systematically studying consequences of hemostatic defects in patients with acute liver failure. We recently demonstrated an intact selleck thrombin generating capacity in plasma from patients with acute liver injury and acute liver failure

(ALI/ALF) despite severely reduced plasma levels of coagulation factors and abnormal routine diagnostic tests of coagulation, such as the prothrombin time.[5] This intact thrombin generation has been ascribed to a concomitant decrease in both procoagulant and anticoagulant factors. In vivo, however, thrombin generation is not only a function of procoagulant and anticoagulant factors, but also of platelets.[6] The platelet surface provides a scaffold for the assembly of coagulation MLN0128 concentration factor complexes, and this assembly is an essential step in the thrombin generation pathway. Primary and secondary hemostasis, therefore, are

integrated physiologically to facilitate thrombin generation and fibrin formation. In view of the physiological importance of platelets in supporting coagulation, we now aim to better define changes in the primary hemostatic system of patients with ALI/ALF and their net effect on bleeding, thrombosis, and disease progression. Our group

initially studied parameters reflecting platelet function by thromboelastography using whole blood of patients with ALI/ALF.[7] We found evidence of normal to increased platelet activity in whole blood of patients with ALI/ALF when compared with normal controls despite reduced platelet numbers in a proportion of patients. The exact mechanisms underlying the observed increase in parameters reflecting platelet function and adhesion are unknown, but it may be attributed to increased levels of the adhesive protein von Willebrand factor (VWF). selleck compound Indeed, we have demonstrated that elevated levels of VWF may (over)compensate for abnormalities in platelet number and function in patients with cirrhosis.[8] These high VWF plasma levels result from disease-related overactivation of the reticulo-endothelial system in endothelial cells.[9, 10] VWF is a large, multimeric protein, and its interaction with platelet glycoprotein Ib is essential for platelet adhesion under conditions of flow, as evidenced by the bleeding tendency associated with qualitative or quantitative defects in VWF in von Willebrand disease. The functional capacity of VWF is normally strictly regulated in the blood by the VWF-cleaving protease, ADAMTS13, as VWF reactivity towards platelets is directly proportional to its multimeric size.

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[1] In acute liver failure, the net effect of all hemostatic chan

[1] In acute liver failure, the net effect of all hemostatic changes is not clear, partly because the changes in the hemostatic system in these patients have been less well defined compared with those in patients with cirrhosis. In an effort to elucidate this issue, we are systematically studying consequences of hemostatic defects in patients with acute liver failure. We recently demonstrated an intact mTOR inhibitor thrombin generating capacity in plasma from patients with acute liver injury and acute liver failure

(ALI/ALF) despite severely reduced plasma levels of coagulation factors and abnormal routine diagnostic tests of coagulation, such as the prothrombin time.[5] This intact thrombin generation has been ascribed to a concomitant decrease in both procoagulant and anticoagulant factors. In vivo, however, thrombin generation is not only a function of procoagulant and anticoagulant factors, but also of platelets.[6] The platelet surface provides a scaffold for the assembly of coagulation Peptide 17 concentration factor complexes, and this assembly is an essential step in the thrombin generation pathway. Primary and secondary hemostasis, therefore, are

integrated physiologically to facilitate thrombin generation and fibrin formation. In view of the physiological importance of platelets in supporting coagulation, we now aim to better define changes in the primary hemostatic system of patients with ALI/ALF and their net effect on bleeding, thrombosis, and disease progression. Our group

initially studied parameters reflecting platelet function by thromboelastography using whole blood of patients with ALI/ALF.[7] We found evidence of normal to increased platelet activity in whole blood of patients with ALI/ALF when compared with normal controls despite reduced platelet numbers in a proportion of patients. The exact mechanisms underlying the observed increase in parameters reflecting platelet function and adhesion are unknown, but it may be attributed to increased levels of the adhesive protein von Willebrand factor (VWF). selleck products Indeed, we have demonstrated that elevated levels of VWF may (over)compensate for abnormalities in platelet number and function in patients with cirrhosis.[8] These high VWF plasma levels result from disease-related overactivation of the reticulo-endothelial system in endothelial cells.[9, 10] VWF is a large, multimeric protein, and its interaction with platelet glycoprotein Ib is essential for platelet adhesion under conditions of flow, as evidenced by the bleeding tendency associated with qualitative or quantitative defects in VWF in von Willebrand disease. The functional capacity of VWF is normally strictly regulated in the blood by the VWF-cleaving protease, ADAMTS13, as VWF reactivity towards platelets is directly proportional to its multimeric size.

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Hepatic intrinsic immunity, referring to a set of cellular-based

Hepatic intrinsic immunity, referring to a set of cellular-based antiviral defense

mechanisms, is a front-line defense against HBV attack. PRRs play a key role in the intrinsic immune response, and the activation of PRRs by agonists contributes to control HBV replication.[3] However, increasing studies have provided evidence that the HBV infection interferes with PRR-mediated antiviral signaling in hepatocytes.[4, 5] For example, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) or HBV virions nearly completely abolished TLR-induced antiviral capacity when pretreated with hepatocytes. Interferon (IFN)-β production and subsequent induction of interferon-stimulated genes, Doxorubicin cost as well as activation of IFN regulatory factor 3 (IRF-3), nuclear factor (NF)-κB, and extracellular signal-regulated kinase (ERK) 1/2, were suppressed by the HBV components.[5] Also, HBV polymerase can interfere with IRF-3 activation and inhibit TLR3-mediated IFN-β induction in hepatocytes.[4] The reduction of TLR2 and TLR4 expression on hepatocytes

from fresh liver biopsies was observed in untreated HBeAg-positive CHB patients, which is associated with a functional decrease in cytokine production.[6, 7] These studies indicate that HBV can target TLRs and downstream signaling and thus attenuate the anti-HBV intrinsic immune responses. Furthermore, the role of the intracellular RIG-I–melanoma differentiation-associated gene 5 (MDA-5) Tamoxifen supplier innate selleck chemicals llc immune system has been focused in HBV infection. HBx protein and HBV polymerase suppress type I IFN production by disrupting the virus-induced signaling

adapter-associated complex and interferes with RIG-I signal pathway in human hepatocytes,[4, 8-10] suggesting that HBV can target the RLR signaling, thereby attenuating the innate antiviral responses. In addition, the intrinsic antiviral defenses can be counteracted by HBx by inhibiting proteasome activities.[11] HBV precore/core proteins downregulates the expression of myxovirus resistance protein A (MxA), an important intrinsic antiviral factor, through direct interaction with MxA promoter.[12] These observations provide more evidence that HBV evolves multiple strategies to evade TLR/RIG-I-mediated antiviral signaling pathways, leading to cell-intrinsic immunotolerance (Fig. 1). Natural killer (NK) cells are important innate immune cells in antiviral immunity. In chronic HBV patients, the function of NK cells is impaired, demonstrated by the decreased number, the declined activation, the hampered IFN-γ production, and the attenuated cytolysis ability. The phenotype of NK cells was found changed, characterized by elevated expression of inhibitory receptor (such as natural killer group 2A [NKG2A]) and downregulated expression of activating receptors (such as CD16, NKG2D, and NKp30).

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