Abstinence-induced cognitive deficits that promote relapse are an

Abstinence-induced cognitive deficits that promote relapse are another key target in the area of medication development. Preclinical studies show that nicotine withdrawal impairs learning and suggest that relapse after smoking withdrawal may occur as an attempt to ameliorate selleck screening library learning-related deficits (Davis, James, Siegel, & Gould, 2005). Atomoxetine, used in the treatment of attention-deficit/hyperactivity disorder, reversed nicotine withdrawal�Cinduced deficits in learning in the mouse contextual fear conditioning model (Davis & Gould, 2007). Although atomoxetine did not alter abstinence-induced cognitive deficits in human smokers, it reduced subjective withdrawal symptoms and cravings to smoke in a subset of smokers (Ray et al., 2009).

New data also suggest that varenicline, an ��4��2 nicotinic acetylcholine receptor (nAChR) antagonist, blocks withdrawal-associated cognitive deficits in mice (Raybuck, Portugal, Lerman, & Gould, 2008). Consistent with this finding, varenicline enhances cognitive performance in abstinent smokers, an effect that may contribute to its efficacy in relapse prevention (Patterson et al., 2009). Other TTURC work has documented effects of nicotine and medications to treat nicotine dependence in a mouse event-related potential (ERP) paradigm (Metzger, Maxwell, Liang, & Siegel, 2007; Siegel et al., 2005). This work is being extended to human ERP models. Developing and validating new models for nicotine dependence medication development is a key goal of the TTURC. Some research focuses on improving models for early human screening (Perkins, Stitzer, & Lerman, 2006).

A recent experiment tested the sensitivity of a within-subject model of medication effects on abstinence and found that intrinsic, but not extrinsic, quit motivation of participants may enhance the validity of brief tests of medication efficacy for smoking cessation (Perkins et al., 2008). Additional studies are exploring the utility of neuroimaging as a tool for identifying smokers at high risk for abstinence-induced craving and to screen new medications for nicotine dependence (Wang et al., 2007). In addition to developing novel treatment approaches and screening models, research at the TTURC seeks to improve the efficacy of existing therapies by identifying likely responders and nonresponders based on genotype. Collaborative pharmacogenetic trials have identified genetic factors predicting treatment outcome, including drug-metabolizing enzymes (Lee et al., 2007; Malaiyandi et al., 2006; F. Patterson, R. A. Schnoll et al., 2008), genes involved in dopaminergic signaling (Colilla et al., 2005; Lerman et al., 2006), AV-951 and nAChRs (Conti et al., 2008).

In a companion paper, Herd, Borland, and Hyland (2009) were able

In a companion paper, Herd, Borland, and Hyland (2009) were able to demonstrate that only some of these beliefs, expectations, and experiences assessed postquitting predict subsequent relapse. Frequency of urges to smoke and low-abstinence self-efficacy selleck products were both strong predictors of relapse, and both of these factors mediated the positive relationships between perceived benefits of smoking and relapse. They also found that the predictive effect of urges to smoke really only emerged after a couple of weeks after quitting, suggesting that it is less important in the period of withdrawal than later on. They found that some experienced losses from quitting predicted relapse, but expectations about health gains from staying quit and reported overall quality of life since quitting did not predict relapse.

In an effort to identify additional predictors of relapse, we sought to extend this work (Herd & Borland, 2009; Herd et al., 2009) by examining other measures of experiences and expectations of quitters using data from a partially overlapping sample collected at subsequent waves of the ITC-4 country project. Our sample did not include data from Waves 1 and 2 as our measures of interest, not considered by Herd et al., were only asked from Wave 3 onwards, and we also had an additional wave (Wave 6) not included in Herd et al. Specifically, our study aimed to explore the extent and predictive value for relapse/quit maintenance of (a) reported changes in capacity to enjoy life��s simple pleasures, (b) ability to cope with stress and control negative emotions, and (c) reported concerns about future smoking related illness despite having quit.

Based on the findings of Herd et al., we hypothesized that reported postquitting gains in life enjoyment and coping with either stress or negative emotions would be associated with sustained abstinence. We did not have any clear prediction for reported concerns about future health, although we suspected that these would be associated with increased relapse risk if they were an indication of ongoing concern that the damage has already been done, and therefore, it is too late to lessen the impact on future health rather than as a continuing motivation to stay quit.

Method Cilengitide The International Tobacco Control Four Country Survey (ITC-4) is a prospective cohort study of a broadly representative sample of over 2,000 adult smokers (18 years and older who reported smoking at least 100 cigarettes in lifetime) conducted in each of four countries: Canada, the United States, the United Kingdom, and Australia. Participants were recruited via random digit dialing telephone interviews and followed up annually. Additional participants were recruited yearly to replace those lost to attrition. A detailed description of the aims and methods of the ITC Project can be found in Thompson et al. (2006).

In all animals, ~90% of all TUNEL+ cells colocalized with macroph

In all animals, ~90% of all TUNEL+ cells colocalized with macrophages despite different apoptosis rates between sellectchem the groups (Fig. 4, A, B, and C). Accordingly, the severalfold elevated apoptosis at 4 wk of reversal resulted in a corresponding increase in infiltrating macrophage numbers within the portal tracts (Supplemental Fig. S4). During this active macrophage recruitment into the resolving scar tissue, no change in the numbers and distribution of lobular (resident) macrophages/Kupffer cells was observed (Supplemental Fig. S4). Fig. 4. Scar-associated macrophages increase at maximal fibrolytic remodeling and colocalize with apoptotic cholangiocytes. A: double immunohistochemistry staining for the macrophage marker CD68 (red, cytoplasmic) and apoptosis (TUNEL: brown, nuclear) on liver …

Mapping of MMP Expression and Activities Reveals a Distinct Subset of MMPs Associated With Fibrosis Reversal Both net interstitial collagenase and gelatinase activities were elevated at maximal scar remodeling (Fig. 1, D and E), indicating that induction and/or activation of the respective MMPs occurred along with diminished expression of their inhibitors, especially TIMP-1 (Fig. 2B). In situ zymography revealed that gelatinase activity was spatially associated with the connective tissue in portal tracts and septa at any time point (Supplemental Fig. S5). To assess the contribution of particular MMPs, we performed gelatin zymography, which showed that, although both gelatinases (MMP-2 and -9) were upregulated at the peak of fibrosis, they demonstrated divergent patterns of regulation during reversal.

MMP-9 was highly upregulated starting at 14 days and peaking at 4 wk of reversal, representing most of gelatinase activity, whereas MMP-2 declined during resolution and was barely detectable at day 7 of reversal (Fig. 5A). Similar results were obtained with immunodetection of MMP-9 protein in liver homogenates by Western blotting (Fig. 5B). MMP activity requires proteolytic activation, which can be achieved by several proteases including plasmin and MMPs themselves (38). We therefore determined transcript levels of MMP-2, -3, -8, -9, -12, -13, -14, and of molecules involved in the plasmin activation cascade, i.e., urokinase plasminogen activator (uPA) and uPA receptor (UPAR)-1, to test whether their expression pattern was consistent with the observed peak of MMP activity and fibrolytic remodeling.

MMP-3, -8, -9, -12, and -14 were most prominently Cilengitide upregulated at those time points that preceded or coincided with peak fibrolytic activity (Fig. 5, A�CC; Fig. 1, D and E). Whereas MMP-12 and -14 transcripts were elevated throughout reversal, MMP-13 transcripts decreased at day 7 and remained slightly elevated above sham-operated controls (Fig. 5C). MMP-8 and -9 mRNA peaked at day 14 (Fig.

Similarly, 297 of the

Similarly, 297 of the Vandetanib CAS 338 (87%) probeset targets hypothesized to be under-expressed in neoplastic tissues were also under-expressed in the validation experiments (P��0.05, MHT); in neoplastic specimens, 247 (73%) of these genes exhibited half or less of the expression seen in normal control tissues. Validation results by phenotype contrast are shown in Table 2. A list of validated up- and down-regulated probesets is shown in Tables S6 and S7, respectively. Table 2 Summary of microarray discovery and validation studies. Quantitative PCR assay for measuring RNA biomarker levels in tissue or plasma One of the most differentially up-regulated probesets in both the discovery (Fig 3A) and validation (Fig 3B) detected transcripts from KIAA1199, a gene of unknown function.

In the validation data set, probeset 1008852-HuGene_st (KIAA1199) was expressed more than 25-fold higher in colorectal neoplasia relative to non-neoplastic controls (Table S6). These results confirmed earlier reports, which found that KIAA1199 mRNA may be a candidate biomarker for colorectal adenoma [14]. Based on our repeated observation of differential expression in neoplastic tissues, the prior evidence of up-regulated expression in both adenomas and cancers and the interesting fact that KIAA1199 has not been previously characterized in terms of structure or function, we chose KIAA1199 to test the idea that tissue expression patterns can be reflected in blood. To further explore the biomarker potential of KIAA1199 we designed a real-time PCR assay for detection of RNA transcripts derived from this locus.

Figure 3 KIAA1199 expression in colon tissue specimens. First, a SYBR-green based real-time PCR for KIAA1199 was used to confirm the tissue validation microarray data; the results were in good agreement with the microarray data for this gene (Fig 3C). Next, KIAA1199 (and GAPDH control) transcript levels were measured in RNA extracted from the plasma fraction of 40 patients with colorectal neoplasia (adenoma or adenocarcinoma) and 20 healthy controls (all categories having been confirmed by clinical pathological findings) using commercially available TaqMan qPCR assays. GAPDH RNA transcripts were detectable in all 60 plasma samples tested (Fig 4A) and moderately higher GAPDH RNA levels were observed in plasma specimens from patients diagnosed with colorectal adenomas or cancer compared to healthy donors (not significant, p values >0.

05). Higher concentrations of KIAA1199 RNA transcripts were detected in plasma from patients with colorectal neoplasia than in plasma Cilengitide from healthy controls (Fig 4B). KIAA1199 RNA was detected in plasma from 31 out of the 40 (77.5%) patients with colorectal neoplasia and in 6 out of the 20 (30%) neoplasia-free patients. Figure 4 Measurement of RNA levels in plasma specimens.

, 2003) Data Analysis We first evaluated participant-rated accep

, 2003). Data Analysis We first evaluated participant-rated acceptability of Dovitinib msds the CD-5As program using descriptive analysis. Second, we evaluated changes in self-reported motivation, self-efficacy, and intention to change among participants receiving the CD-5As program using paired samples t tests. Third, we examined the proportion of participants assigned to CM-Lite who actively participated in the incentive program, as well as the frequency of success and subjective responses to CM-Lite among those who did participate. Fourth, following evaluation of the success of randomization, we examined differences in abstinence between experimental conditions (CD-5As, CM-Lite, and combined) and the control condition using logistic regression with the categorical covariates procedure.

All analyses were on an intent -to-treat basis that analyzed participants as allocated to condition without respect to completion of treatment elements. These analyses controlled for level of smoking at baseline as well as any variables found to differ between groups at p �� .10 (with unadjusted analyses also presented). Secondary analyses of intervention effects on help-seeking and sustained abstinence were also conducted. Finally, we collapsed across conditions in order to compare participants receiving CD-5As (with or without CM-Lite) with those who did not. These collapsed groups are hereafter referred to as ��intervention groups�� in order to distinguish them from conditions defined above.

Results A total of 1,317 participants were screened between July of 2008 and November of 2009; 1,207 were excluded, primarily due to being beyond 27-week gestation or denying smoking in the past week (Figure 1). The trial ended after 110 participants were randomized. These 110 randomized participants (26 in CD-5As, 28 in CM-Lite, 30 in the combined condition, and 26 in TAU) averaged 27.9 (SD = 6.4) years of age, with a range of 18�C44; a total of 90 (81.8%) were Black, with one participant reporting Hispanic ethnicity. Cigarettes per day in the week prior to recruitment averaged 8.0 (SD = 8.2, range = 1�C50). A total of 57 participants (52.8%) scored above the FTND cutoff for nicotine dependence. See Table 1 for details on baseline participant characteristics and differences between conditions on those variables. There were no significant differences between conditions on any of the baseline characteristics examined, although one variable (minority vs.

nonminority race) was below p = .10 and so was controlled for in subsequent analyses. There were no site differences on any baseline or demographic variables, so subsequent analyses collapsed across site. Table 1. Sample Characteristics Carfilzomib at Baseline by Condition (N = 110) Figure 1. Participant flow. Follow-up evaluation took place between January of 2009 and January of 2010 at a mean of 10.1 (SD = 3.9) weeks postrandomization/intervention; a total of 94 (85.

An extrapolation of this framework to human addiction suggests th

An extrapolation of this framework to human addiction suggests that environments (or neighborhoods) with numerous resources would be associated with less stress and thus less drug addiction, whereas deprived environments would be associated with greater stress and drug addiction. In fact, research among racially/ethnically diverse smokers has confirmed a significant selleckbio prospective relationship between neighborhood problems and neighborhood vigilance and increased negative affect/stress (Businelle et al., 2010), and numerous human studies have linked negative affect and stress to smoking behaviors and smoking cessation (e.g., Kenford et al., 2002; Shiffman & Waters, 2004).

Other potential mechanisms connecting neighborhood environments and smoking behaviors could include the increased presence of smoking cues in less desirable neighborhoods, such as a greater density of tobacco retail outlets and more tobacco advertising (cf. Schneider, Reid, Peterson, Lowe, & Hughey, 2005; Siahpush, Jones, Singh, Timsina, & Martin, 2010a, 2010b). Tobacco retail outlet density has been associated with the number of cigarettes consumed per day among smokers in at least one prior study (Chuang, Cubbin, Ahn, & Winkleby, 2005). Thus, subjective perceptions of problems or the need for increased vigilance in the neighborhood might affect tobacco dependence among smokers through motives such as the relief of negative affect/stress or by evoking greater physiological cravings to smoke in response to smoking cues.

Increasing understanding of relations between neighborhood perceptions and tobacco dependence is an important first step in better understanding the influence of the neighborhood environment on smoking behaviors. To our knowledge, only one study has examined the impact of neighborhood perceptions on nicotine dependence. Specifically, Sapag et al. (2010) found that trust among neighbors was inversely associated with the number of cigarettes smoked per day among Chilean smokers. However, no previous studies have examined the association between the neighborhood context and smoking dependence among vulnerable minority groups in the United States, such as African Americans (AAs). A better understanding of the relations between the neighborhood environment and tobacco dependence among this population is important, as AA smokers are more likely to incur tobacco-related diseases and die from these diseases than their Caucasian counterparts, despite the later initiation of smoking and lower smoking rates (i.e., cigarettes consumed per day) than Caucasian smokers (American Cancer Society, 2009; Vidrine et al., 2009a, 2009b). In addition, AA smokers may also be less likely to successfully quit smoking Cilengitide than Caucasians (Fu et al.

After 6h of incubation, radioactivity of the supernatant (100��l)

After 6h of incubation, radioactivity of the supernatant (100��l) was measured with a ��-counter. The percentage of specific lysis=100 �� (experimental c.p.m.?spontaneous c.p.m.)/(maximum c.p.m.?spontaneous c.p.m.). Flow cytometry For the expression of CD247 (transducing �� molecule) on NK cells, PBMCs were selleck Ruxolitinib stained with CD56-FITC (DAKO, Glostrup, Denmark) and CD3-APC (DAKO). Thereafter, the stained cells were fixed with 0.25% formaldehyde in PBS for 10min, followed by permeabilisation with digitonin (Invitrogen, Carlsbad, CA, USA; 10��gml?1) for 15min on ice, and stained with anti-CD247 mAbs conjugated with PE (IMMUNOTEC, Marseille, France) or with IgG1 isotype control mAbs for 10min on ice. The mean fluorescence intensity for CD247 gated on CD56(+)CD3(?) cells was assessed by flow cytometric analysis.

For the expression of perforin and granzyme-B on NK cells, PBMCs were stained with CD56-FITC and CD3-APC. Thereafter, the stained cells were fixed and permeabilised using the Cytoperm/Cytofix kit (BD Bioscience, San Diego, CA, USA), followed by staining with mouse anti-human perforin mAbs conjugated with FITC (BD Pharmingen, San Diego, CA, USA) or mouse anti-human Granzyme-B mAbs conjugated with FITC (BD Pharmingen). The mean fluorescence intensity for perforin or granzyme-B gated on CD56(+)CD3(?) cells was assessed by flow cytometric analysis. For the expression of IL-21 receptor (IL-21R) on NK cells, PBMCs were stained with CD56-FITC, CD3-APC, and PE-labelled anti-human IL-21R mAb (R&D Systems, Minneapolis, MN, USA).

Statistical analysis Paired and non-paired Student’s t-tests were used to examine AV-951 the differences between groups. Findings were considered significant when P-values were <0.05. Results Trastuzumab- and Cetuximab-mediated ADCC was impaired in patients with ESCC We examined Trastuzumab- and Cetuximab-mediated ADCC of PBMCs derived from patients and healthy donors. High EGFR-expressing KYSE30 and low EGFR-expressing KYSE110 were killed by Cetuximab-mediated ADCC, and the ADCC activity reflected the degree of EGFR expression, as shown in Figure 1A (high EGFR-expressing KYSE30 vs low EGFR-expressing KYSE110). It is noteworthy that the levels of Cetuximab-mediated ADCC in patients with ESCC were significantly impaired in comparison with those in healthy donors (Figure 1A), in line with our previous reports (Kawaguchi et al, 2007a). Figure 1 Trastuzumab- and Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells (PBMCs) from patients and healthy donors. (A) Cetuximab-mediated ADCC of PBMCs from patients (oesophageal squamous cell carcinoma …

Taken together, our novel data show that inhibition

Taken together, our novel data show that inhibition http://www.selleckchem.com/products/kpt-330.html of Rho-kinase signalling ameliorates tissue damage in pancreatitis. Indeed, our findings show that Rho-kinase regulates trypsinogen activation in pancreatitis and that interference with Rho-kinase activity decreased MIP-2 formation, neutrophil activation (Mac-1 expression) and recruitment in the pancreas. Thus, our results not only elucidate important signalling mechanisms in pancreatitis but also suggest that targeting Rho-kinase activity may be a useful approach to protect against pathological tissue damage in SAP.

Acknowledgments This work was supported by grants from the Swedish Medical Research Council (2009-4872), Crafoordska stiftelsen, Einar och Inga Nilssons stiftelse, Harald och Greta Jaenssons stiftelse, Greta och Johan Kocks stiftelser, Fr?ken Agnes Nilssons stiftelse, Franke och Margareta Bergqvists stiftelse f?r fr?mjande av cancerforskning, Magnus Bergvalls stiftelse, Mossfelts stiftelse, Nanna Svartz stiftelse, Ruth och Richard Julins stiftelse, Svenska L?kares?llskapet, Allm?na sjukhusets i Malm? stiftelse f?r bek?mpande av cancer, MAS fonder, Malm? University Hospital and Lund University. D Awla and A Abdulla are supported by a fellowship from the Kurdistan regional government and the Nanakali Group. Glossary Abbreviations i.p. intraperitoneal MIP-2 macrophage inflammatory protein-2 MNL monomorphonuclear leucocytes MPO myeloperoxidase MOPS 3-(morpholino) propanesulphonic acid PBS phosphate-buffered saline PMNL polymorphonuclear leucocytes RIA radioimmunoassay SAP severe acute pancreatitis TAP trypsinogen activating peptide Conflict of interest The authors state no conflict of interest.

Supporting Information Teaching Materials; Figs 1�C7 as PowerPoint slide. Click here to view.(459K, pptx)
The overall survival (OS) time of patients with metastatic colorectal cancer (CRC) has increased owing to novel therapeutic strategies combining chemotherapy with monoclonal antibodies against vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR). Whereas mutations in the k-ras oncogene predict outcome to EGFR antibody treatment in patients with metastatic CRC (Lievre et al, 2006; Karapetis et al, 2008), equivalent biomarkers for the VEGF antibody, bevacizumab, are currently lacking (Jubb et al, 2006b; Sessa et al, 2008), mainly because the specific molecular determinants of clinical response and resistance to the drug are unknown. Similarly, there are currently no established biomarkers predicting outcome to chemotherapy in CRC (De Roock et al, 2009). Originally, it Brefeldin_A was anticipated that traditional markers of tumour angiogenesis would predict outcome to bevacizumab.

CD has been shown to play important roles in eukaryotic cell func

CD has been shown to play important roles in eukaryotic cell functioning and tissue turnover and remodeling, being involved in protein maturation and degradation nothing and in cell death as well as in cell proliferation [61]�C[63]. On this ground, it is expected that the lack of CD altered the autophagy flux and the rate of cell death vs cell proliferation in several organs in T-MPO zebrafish. Investigations in this direction are underway in our laboratory. Defective ontogenesis of the swim bladder, altered development of the eye and of the retina, defective absorption of the yolk and shortened lifespan have been reported in zebrafish carrying inactivating mutations in genes involved in the biogenesis, trafficking and fusion of endosomes, lysosomes and lysosome related organelles [35], [36], [49], [64].

The similarities of these phenotypes underscore the role of lysosomal proteolysis in development. In conclusion, the present findings show that CD plays critical roles in tissue homeostasis and organ development in zebrafish. Given the similarity of organ development, organization and function between zebrafish and mammals [30], these data suggest that defective CD-mediated lysosomal proteolysis may contribute to several pathologies in humans also, including the blinding diseases, such as the Leber’s congenital amaurosis, the Best macular dystrophy and the age-related macular degeneration, in which the RPE layer is primarily affected [65], [66]. In this respect, it is worth noting that defective CD activity in human RPE cells has been linked to age-related macular degeneration [67], [68].

Materials and Methods Zebrafish husbandry Zebrafish (Danio rerio) were maintained as previously described [34] and staged based on developmental time and morphological criteria according to published guidelines [39], [48]. Fish were kept under a 14 hours-light and 10 hours-dark photoperiod at approximately 28��C. Following fertilization, eggs were collected and embryos (wild type or micro-injected) were raised at 28��C under standard laboratory conditions. Unless otherwise specified, embryos were grown in the presence of 0.003% 1-phenyl-2-thiourea (PTU) to prevent formation of melanin pigment. Experimental procedures related to fish manipulation followed the recommendation reported in [69] and were conform to the Italian regulations protecting animals used for research purposes, including those of the DL 116/92.

Reverse-Transcription Polymerase Chain Reaction Total RNA was extracted according to the TRIzol LS reagent protocol (Invitrogen Co, Carlsbad, CA, US) from UFE, embryos at 30% epiboly (corresponding to approximately 4.66 hpf), or at 1 and Cilengitide 2 dpf and larvae at 3 and 4 dpf (n=50 of each sample). Aliquots (3.5 ��g) of DNAse I-treated total RNA were retro-transcribed using the RevertAiD H Minus First Strand cDNA Synthesis Kit (Fermentas, Burlington, CA, US).

Individual subjects with HBV infection were confirmed positive fo

Individual subjects with HBV infection were confirmed positive for HBsAg and selleck bio detectable HBV virions for at least 12 months [24]. Subjects with positive hepatitis C and D, HIV infection, with autoimmune hepatitis or metabolic liver disease, receiving immunosuppressive therapy, or antiviral therapy within the past 12 months before entry were excluded [24]. All of the patients denied to being drug users, or having been exposed to hepatotoxin [24]. Those HBV infected subjects were further classified into two distinct groups, according to the levels of serum HBV DNA loads and ALT. Subjects with high copies of serum HBV DNA loads and normal levels of ALT (normal range: ��40 U/L) were considered as IT, but those with relatively low levels of serum HBV DNA loads and abnormal levels of ALT were defined as IA, as described previously [6]�C[8], [25].

Their demographic and clinical characteristics are summarized in Table 1. Those IA patients were treated orally with 10 mg of adefovir dipivoxil (Gilead Science, Forster City, USA) daily for 12 weeks. Their serum ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb concentrations, and HBV DNA loads were analyzed (Table 2). Individual IA patients with at least 100-fold reduced serum HBV viral loads were defined as drug response patients, but others were defined as drug non-response patients. The study conformed for the guidelines of the Declaration of Helsinki and was approved by Human Ethics Committee of Jilin University,ChangChun,China. Written informed consent was obtained from each participant.

Peripheral blood samples were obtained from individual subjects, and the levels of serum AST and ALT were detected by Biochemistry Automatic Analyzer (Roche Diagnostics, Branchburg, USA) [22]. The levels of serum HBV DNA loads were measured by quantitative PCR assay using the luciferase quantization detection kit with a detection limit of 300 copies/mL (Roche Amplicor, Basel, Switzerland), according to the manufacturers’ instruction [22]. The levels of HBV-related HBsAg, HBsAb, HBeAg, and HBeAb were determined by a chemiluminescent microparticle immunoassay (CMIA) using an Abbott I 2000 automated chemiluminescence immunoassay analyzer (Abbott Laboratories, Abbott Park, Illinois, USA). The concentrations of serum HBeAb in individual samples were determined semi-quantitatively by a competitive inhibition method, according to the manufacturers’ instruction and a previous report [26].

The data are expressed as median (range) of signal OD to cut-off (S/CO). Accordingly, the higher concentrations of Batimastat serum HBeAb, the lower values of S/CO. Mice Both female and male C57BL/6 HBV-transgenic mice and non-transgenic C57BL/6 mice at 8 weeks of age were purchased from Vital River Laboratories (Beijing, China). This HBV-transgenic line of mice displays high levels of serum HBV replicative DNA, with the log value of the HBV DNA load [5.94, (5.45�C6.