L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment also ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NFκB production. Conclusion: H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of Small molecule library in vitro L. acidophilus pre-treatment reduce H. pylori-induced inflammation through inactivation of the Smad7 and NFκB pathways. Key Word(s): 1. H. pylori; 2. probiotics; 3. Smad7; 4. NFκB; Presenting Author: YONG XIE Additional Authors: ZHIFA LV, BEN WANG, HUILIE ZHENG Corresponding Author:

YONG XIE Affiliations: Digestive Disease Institute, the First Affiliated Hospital of Nanchang University, Nanchang, China.; Public Health College of Nanchang University Objective: Several studies have reported that the application of probiotics during the eradication of H.pylorican improve Pirfenidone the eradication rates and reduce the therapy-associated side. To determine whether the probiotics could help to improve the eradication rates and reduce side effects, and to investigate the appropriate time to add the probiotics during anti-H. pylori treatment. Methods: By searching PUBMED, EMBASE,

SCI, CKNI and Wanfang Databases, we selected all the randomized controlled trials (RCTs) comparing 上海皓元医药股份有限公司 probiotics supplementation to placebo or no treatment during anti-H. Pylori regimens for meta analysis. Statistical analysis was performed with the Stata version 12.0 software. Subgroup analysis and sensitivity analysis were also carried out. Results: 55 RCTs involving a total of 8449 participants met the inclusion criteria. Compared with the non-probiotics anti-H. pylori regimens, probiotics significantly increased the eradication rate. The pooled RR by intention-to-treat and

by perprotocol analysis in the probiotics supplementation versus without probiotics was 1.15[95% confidence interval (CI), 1.12–1.19] and1.14 (95% CI, 1.11–1.17), respectively. And reduced the risk of overall H. pylori therapy related adverse effects (RR0.48, 95% CI,0.38–0.60). In addition, There are no significant differences for the eradication rate of H. pylori whenever you add probiotics. The pooled RR(itt) is 1.17 (95% CI, 1.09–1.26) (using probiotics as a pretreatment),1.14 (95% CI, 1.10–1.19) (using probiotics after regular non-probiotics therapy), 1.16 (95% CI, 1.10–1.21) (using probiotics in the same time with the regular non-probiotics therapy). Conclusion: The supplementation with probiotics during H. pylori eradication therapy may be effective in increasing eradication rates and decreasing therapy-related side effects. In addition, the probiotics may have similar effects on eradication rates whenever they are added. Key Word(s): 1. Helicobacter pylori; 2. Probiotics; 3. Meta-analysis; 4.

We analysed data presented by Pearre & Maass

(1998) and found that cats sampled from sites close to human habitation (farms, suburban and urban studies) take significantly smaller prey (23.2 ± 8.3 g; n = 16 studies) than cats in rural areas (72.6 ± 92.1 g, n = 28 studies). These data suggest that cats living close to human LY294002 in vitro habitation modify their diet, which may explain how these hypercarnivores deal so well in anthropogenic environments. The ‘ideal’ urban carnivore should be highly adaptable in terms of diet, movement patterns and social behaviour (in the section: ‘How is the ecology of mammal carnivores influenced by urban living?’). However, there are some exceptions to this premise. For example, Herr et al. (2009a) found that stone martens in Luxembourg were almost entirely urban (their territories falling within the extent of the study towns), and their presence suggests that they successfully deal with the challenges of this environment. Their socio-spatial distribution, however, is almost exactly the same as recorded in non-urban habitats, and stone martens do not make much use of anthropogenic food sources (implying both social and dietary inflexibility). While stone martens are

well-established urban carnivores, the congeneric pine marten Martes martes avoids human habitation (Baghli et al., 2002; Herr, 2008). This difference Staurosporine supplier appears to be due to pine martens being less omnivorous than stone martens, and while pine martens are diurnal, the crepuscular stone marten is less susceptible to clashes with humans (Herr, 2008; Herr, Schley & Roper, 2009b). Cardillo et al. (2004) demonstrated how

biological features (e.g. geographic range, population density, reproductive rates and dietary requirements) explain 45% of variation in risk of extinction for carnivore species, or 80% when combined with high levels of exposure to human populations. Biological ‘inflexibility’ (small geographic ranges, low population density, low reproductive rates, need for 上海皓元医药股份有限公司 large hunting areas or specific prey) in the face of increasing human populations and urbanization means potential extinction, while ‘flexible’ species (wide geographic range, potential high population density, high reproduction and generalist trophic niche) are more likely to adapt to increasing urbanization. Although urban carnivores may be valued by large sectors of society (Baker & Harris, 2007) and even encouraged (e.g. through deliberate feeding section: ‘What do they eat?’), these animals can also clash with their human neighbours to a greater or lesser degree through disease transmission to humans and pets, damage to houses and gardens, general nuisance value (e.g. bin-raiding) or direct attack of humans or pets (Baker & Harris, 2007). The risk of zoonoses is a significant cause for concern. The public health issues of carnivore presence in cities have therefore been the focus of much research as well as the drive for extensive control measures.

Prenatal diagnosis confirmed that four foetuses were normal and all of them born normally. However, two foetuses had been identified as abnormal and undergone abortion. Compared with LD-PCR, modified I-PCR is more rapid and convenient for detecting the FVIII Inv22 in genetic diagnosis. It is recommended that a patient undergoes both

modified I-PCR (to detect the FVIII Inv22) and biochemical assay (to measure the FVIII activity of umbilical cord blood) in prenatal diagnosis. When we have more experience, the DNA samples from chorionic villus or amniotic fluid can be analysed for prenatal diagnosis using the modified I-PCR alone. “
“Summary.  Prophylactic treatment is recommended for severe Tamoxifen supplier haemophilia. Non-adherence to a prophylactic regimen can limit treatment effectiveness and compromise outcomes. The aim of this study is

to validate a new prophylactic treatment adherence scale entitled Validated see more Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS-Pro), a self-/parent-report questionnaire consisting of 24 questions on six (four-item) subscales (Time, Dose, Plan, Remember, Skip, Communicate) that takes approximately 10 min to complete and is currently available in English only. Participants were recruited to complete the VERITAS-Pro for validation and reliability analysis; and observers were recruited for inter-rater reliability analysis. Validation measures included subjective adherence ratings from participants and providers and the total number of recommended infusions administered as obtained from infusion logs. Data were evaluated for the entire sample and for parent-report and self-report subsamples. The study sample included 67 males, MCE 53 (79.1%) diagnosed with severe FVIII deficiency. Internal consistency for the total VERITAS-Pro score and all subscales was good to excellent; test-retest reliability correlations were very strong. Validation measures were strongly correlated with VERITAS-Pro scores. The VERITAS-Pro is a reliable and valid measure of adherence to prophylactic treatment of haemophilia. The VERITAS-Pro has greater utility than a global

or informal rating of adherence because it represents a quantified and validated measure of adherence from the patient’s perspective and it divides adherence into specific areas, allowing insight into particular issues underlying non-adherence. This tool may increase sensitivity to adherence problems and allow more targeted interventions to enhance adherence. “
“This review summarizes the current knowledge of the immunological mechanisms that are responsible for the development of antibodies against factor VIII in patients with hemophilia A who receive replacement therapy. The generation of high affinity antibodies against protein antigens such as FVIII is believed to require cognate interactions between B cells and CD4+ helper T cells.

Prenatal diagnosis confirmed that four foetuses were normal and all of them born normally. However, two foetuses had been identified as abnormal and undergone abortion. Compared with LD-PCR, modified I-PCR is more rapid and convenient for detecting the FVIII Inv22 in genetic diagnosis. It is recommended that a patient undergoes both

modified I-PCR (to detect the FVIII Inv22) and biochemical assay (to measure the FVIII activity of umbilical cord blood) in prenatal diagnosis. When we have more experience, the DNA samples from chorionic villus or amniotic fluid can be analysed for prenatal diagnosis using the modified I-PCR alone. “
“Summary.  Prophylactic treatment is recommended for severe learn more haemophilia. Non-adherence to a prophylactic regimen can limit treatment effectiveness and compromise outcomes. The aim of this study is

to validate a new prophylactic treatment adherence scale entitled Validated GDC-0449 cell line Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS-Pro), a self-/parent-report questionnaire consisting of 24 questions on six (four-item) subscales (Time, Dose, Plan, Remember, Skip, Communicate) that takes approximately 10 min to complete and is currently available in English only. Participants were recruited to complete the VERITAS-Pro for validation and reliability analysis; and observers were recruited for inter-rater reliability analysis. Validation measures included subjective adherence ratings from participants and providers and the total number of recommended infusions administered as obtained from infusion logs. Data were evaluated for the entire sample and for parent-report and self-report subsamples. The study sample included 67 males, MCE公司 53 (79.1%) diagnosed with severe FVIII deficiency. Internal consistency for the total VERITAS-Pro score and all subscales was good to excellent; test-retest reliability correlations were very strong. Validation measures were strongly correlated with VERITAS-Pro scores. The VERITAS-Pro is a reliable and valid measure of adherence to prophylactic treatment of haemophilia. The VERITAS-Pro has greater utility than a global

or informal rating of adherence because it represents a quantified and validated measure of adherence from the patient’s perspective and it divides adherence into specific areas, allowing insight into particular issues underlying non-adherence. This tool may increase sensitivity to adherence problems and allow more targeted interventions to enhance adherence. “
“This review summarizes the current knowledge of the immunological mechanisms that are responsible for the development of antibodies against factor VIII in patients with hemophilia A who receive replacement therapy. The generation of high affinity antibodies against protein antigens such as FVIII is believed to require cognate interactions between B cells and CD4+ helper T cells.

Prenatal diagnosis confirmed that four foetuses were normal and all of them born normally. However, two foetuses had been identified as abnormal and undergone abortion. Compared with LD-PCR, modified I-PCR is more rapid and convenient for detecting the FVIII Inv22 in genetic diagnosis. It is recommended that a patient undergoes both

modified I-PCR (to detect the FVIII Inv22) and biochemical assay (to measure the FVIII activity of umbilical cord blood) in prenatal diagnosis. When we have more experience, the DNA samples from chorionic villus or amniotic fluid can be analysed for prenatal diagnosis using the modified I-PCR alone. “
“Summary.  Prophylactic treatment is recommended for severe Bioactive Compound Library research buy haemophilia. Non-adherence to a prophylactic regimen can limit treatment effectiveness and compromise outcomes. The aim of this study is

to validate a new prophylactic treatment adherence scale entitled Validated selleck chemicals llc Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS-Pro), a self-/parent-report questionnaire consisting of 24 questions on six (four-item) subscales (Time, Dose, Plan, Remember, Skip, Communicate) that takes approximately 10 min to complete and is currently available in English only. Participants were recruited to complete the VERITAS-Pro for validation and reliability analysis; and observers were recruited for inter-rater reliability analysis. Validation measures included subjective adherence ratings from participants and providers and the total number of recommended infusions administered as obtained from infusion logs. Data were evaluated for the entire sample and for parent-report and self-report subsamples. The study sample included 67 males, 上海皓元 53 (79.1%) diagnosed with severe FVIII deficiency. Internal consistency for the total VERITAS-Pro score and all subscales was good to excellent; test-retest reliability correlations were very strong. Validation measures were strongly correlated with VERITAS-Pro scores. The VERITAS-Pro is a reliable and valid measure of adherence to prophylactic treatment of haemophilia. The VERITAS-Pro has greater utility than a global

or informal rating of adherence because it represents a quantified and validated measure of adherence from the patient’s perspective and it divides adherence into specific areas, allowing insight into particular issues underlying non-adherence. This tool may increase sensitivity to adherence problems and allow more targeted interventions to enhance adherence. “
“This review summarizes the current knowledge of the immunological mechanisms that are responsible for the development of antibodies against factor VIII in patients with hemophilia A who receive replacement therapy. The generation of high affinity antibodies against protein antigens such as FVIII is believed to require cognate interactions between B cells and CD4+ helper T cells.

CBF estimates are known to differ between the two techniques simply due of the difference in diffusion behavior between the two tracers employed.[27] http://www.selleckchem.com/screening/protease-inhibitor-library.html Additionally, calculations of DSC measurements assume that the tracer stays completely intravascular, which is not actually true in the case of high grade lesions and resultant blood brain barrier breakdown; however, in the current study we employed a preload along with posthoc leakage-correction algorithms.[2, 8-10] Additionally, while great care was taken to properly align patient low resolution ASL data with high resolution anatomical and DSC data, misregistration between these data

sets may have potentially confounded the voxel-wise coherence between the two modalities. Routine use of ASL

for the see more assessment of brain tumor perfusion has not been established in the clinic, mostly due to relatively long acquisition times, lower image resolution, lower SNR, sensitivity to motion artifacts, and limited brain coverage. The advent of 3D PCASL with the use of background suppression at high field strengths has bridged this apparent gap, allowing higher resolution and higher SNR in shorter periods of time. Thus, the use of high resolution 3D PCASL with background suppression is a suitable option for evaluating brain tumor perfusion in patients with renal compromise; however, the administration of exogenous contrast agents remain the most advantageous image sequence for the clinical evaluation of brain tumors (eg, postcontrast T1-weighted images) and therefore the use of DSC-MRI during dynamic injection of contrast will remain an important sequence for evaluating tumor perfusion. Grant Support: UCLA Institute for Molecular Medicine Seed Grant (BME); UCLA Radiology Exploratory Research Grant

(BME); Brain Tumor Funders Collaborative (WBP); Art of the Brain (TFC); Ziering Family Foundation in memory of Sigi Ziering (TFC); Singleton Family Foundation (TFC); Clarence Klein Fund for Neuro-Oncology (TFC). “
“We investigated a simple MCE公司 imaging sign for Alzheimer’s disease (AD), using diffusion tensor imaging (DTI). We hypothesized that a reduction in fractional anisotropy (FA) in the fornix could be utilized as an imaging sign. Twenty-three patients with AD, 24 patients with amnestic mild cognitive impairment (aMCI), and 25 control participants (NC) underwent DTI at baseline and 1 year later. The diagnosis was reevaluated 1 year and 3 years after the initial scan. A color-scaled FA map was used to visually identify the FA reduction (“fornix sign”). We investigated whether the fornix sign could separate AD from NC, and could predict progression from aMCI to AD or NC to aMCI. We also quantified FA of the fornix to validate the fornix sign. The fornix sign was identical to the lack of any voxels with an FA > .

CBF estimates are known to differ between the two techniques simply due of the difference in diffusion behavior between the two tracers employed.[27] LEE011 in vitro Additionally, calculations of DSC measurements assume that the tracer stays completely intravascular, which is not actually true in the case of high grade lesions and resultant blood brain barrier breakdown; however, in the current study we employed a preload along with posthoc leakage-correction algorithms.[2, 8-10] Additionally, while great care was taken to properly align patient low resolution ASL data with high resolution anatomical and DSC data, misregistration between these data

sets may have potentially confounded the voxel-wise coherence between the two modalities. Routine use of ASL

for the Doxorubicin solubility dmso assessment of brain tumor perfusion has not been established in the clinic, mostly due to relatively long acquisition times, lower image resolution, lower SNR, sensitivity to motion artifacts, and limited brain coverage. The advent of 3D PCASL with the use of background suppression at high field strengths has bridged this apparent gap, allowing higher resolution and higher SNR in shorter periods of time. Thus, the use of high resolution 3D PCASL with background suppression is a suitable option for evaluating brain tumor perfusion in patients with renal compromise; however, the administration of exogenous contrast agents remain the most advantageous image sequence for the clinical evaluation of brain tumors (eg, postcontrast T1-weighted images) and therefore the use of DSC-MRI during dynamic injection of contrast will remain an important sequence for evaluating tumor perfusion. Grant Support: UCLA Institute for Molecular Medicine Seed Grant (BME); UCLA Radiology Exploratory Research Grant

(BME); Brain Tumor Funders Collaborative (WBP); Art of the Brain (TFC); Ziering Family Foundation in memory of Sigi Ziering (TFC); Singleton Family Foundation (TFC); Clarence Klein Fund for Neuro-Oncology (TFC). “
“We investigated a simple 上海皓元医药股份有限公司 imaging sign for Alzheimer’s disease (AD), using diffusion tensor imaging (DTI). We hypothesized that a reduction in fractional anisotropy (FA) in the fornix could be utilized as an imaging sign. Twenty-three patients with AD, 24 patients with amnestic mild cognitive impairment (aMCI), and 25 control participants (NC) underwent DTI at baseline and 1 year later. The diagnosis was reevaluated 1 year and 3 years after the initial scan. A color-scaled FA map was used to visually identify the FA reduction (“fornix sign”). We investigated whether the fornix sign could separate AD from NC, and could predict progression from aMCI to AD or NC to aMCI. We also quantified FA of the fornix to validate the fornix sign. The fornix sign was identical to the lack of any voxels with an FA > .

The groups were otherwise well balanced. Patients from group B (n = 7) underwent a

pre-sorafenib MRI scan, with a maximum of 32 days before initiation of sorafenib (median, 18; range, 8-32) and a maximum of 53 days before Y90 (median, 42; range, 21-53). Median time from baseline MRI to Y90 procedure for group A was 18 days (range, 14-42). Seven of the eight patients in group B had a baseline MRI scan on the day of Y90 treatment immediately preceding the procedure, translating into a median time from imaging to Y90 of 0 days. For both groups, the pre-Y90 MRI scan served as the baseline. Median time from last MRI scan to transplant was 25 days (range, 5-93). Findings on the last pre-OLT scan were consistent with the 3-month scan for all 16 lesions. CPN as well PLX4032 concentration as 50%-99% and <50% necrosis was observed in 6 (67%), 1 (11%), and 2 (22%) tumors in group A and 3 (42%), 2 (28%), and 2 (28%) in group B, respectively (P = 0.41; Table 2). Grouping all tumors, response by size criteria was observed by RECIST (P = 0.08) and WHO (P = 0.06), despite failing to Tigecycline cost reach significance (Fig. 2). Corrected P value of Wilcoxon’s test, comparing 1 month post-Y90 to baseline, showed a significant reduction of

WHO (P = 0.047), but failed to reach significance for RECIST (P = 0.077). Compared to baseline, a significant decrease in enhancing tumor diameter (P < 0.01 MCE and 0.03) and the sum of the longest and largest viable tumor diameter (P < 0.01 and 0.03) was observed at 1 and 3 months, suggesting that EASL and mRECIST were equivalent (Fig. 2). At 1 month,

CRs by EASL and mRECIST were noted in 4 of 16 lesions; these corresponded to CPN in 2 of 4 of cases. At 3 months, CRs by EASL and mRECIST were noted in 7 of 14; this corresponded to CPN in 3 of 7 of cases (Table 2; Fig. 3). At 1 month, PRs by EASL and mRECIST were noted in 8 of 16 lesions; these corresponded to CPN in 5 of 8 of cases. At 3 months, PRs by EASL and mRECIST were noted in 3 of 14 and 4 of 14 lesions; this corresponded to CPN in 1 of 3 and 2 of 4 cases (Table 2; Fig. 3). Compared to baseline, ADC (P = 0.46) values did not differ at 1 or 3 months (Fig. 2). With response defined as an ADC increase ≥5% from baseline, 9 of 15 and 8 of 12 lesions were classified as responders at 1 and 3 months, respectively (Table 2), but without being able to predict pathological results. CPN as well as 50%-99% and <50% necrosis were observed in 5, 3, and 1 ADC responding lesions and 4, 1, and 1 ADC nonresponding lesions at 1 month (P = 0.47); at 3 months, it was 4, 2, and 2 ADC responding lesions and 2, 1, and 1 ADC nonresponding lesions (P = 0.73; Fig. 3). The subjective response assessment showed good results in predicting pathological results, particularly for one of the investigators (F.M.

The groups were otherwise well balanced. Patients from group B (n = 7) underwent a

pre-sorafenib MRI scan, with a maximum of 32 days before initiation of sorafenib (median, 18; range, 8-32) and a maximum of 53 days before Y90 (median, 42; range, 21-53). Median time from baseline MRI to Y90 procedure for group A was 18 days (range, 14-42). Seven of the eight patients in group B had a baseline MRI scan on the day of Y90 treatment immediately preceding the procedure, translating into a median time from imaging to Y90 of 0 days. For both groups, the pre-Y90 MRI scan served as the baseline. Median time from last MRI scan to transplant was 25 days (range, 5-93). Findings on the last pre-OLT scan were consistent with the 3-month scan for all 16 lesions. CPN as well find more as 50%-99% and <50% necrosis was observed in 6 (67%), 1 (11%), and 2 (22%) tumors in group A and 3 (42%), 2 (28%), and 2 (28%) in group B, respectively (P = 0.41; Table 2). Grouping all tumors, response by size criteria was observed by RECIST (P = 0.08) and WHO (P = 0.06), despite failing to AZD6244 reach significance (Fig. 2). Corrected P value of Wilcoxon’s test, comparing 1 month post-Y90 to baseline, showed a significant reduction of

WHO (P = 0.047), but failed to reach significance for RECIST (P = 0.077). Compared to baseline, a significant decrease in enhancing tumor diameter (P < 0.01 上海皓元 and 0.03) and the sum of the longest and largest viable tumor diameter (P < 0.01 and 0.03) was observed at 1 and 3 months, suggesting that EASL and mRECIST were equivalent (Fig. 2). At 1 month,

CRs by EASL and mRECIST were noted in 4 of 16 lesions; these corresponded to CPN in 2 of 4 of cases. At 3 months, CRs by EASL and mRECIST were noted in 7 of 14; this corresponded to CPN in 3 of 7 of cases (Table 2; Fig. 3). At 1 month, PRs by EASL and mRECIST were noted in 8 of 16 lesions; these corresponded to CPN in 5 of 8 of cases. At 3 months, PRs by EASL and mRECIST were noted in 3 of 14 and 4 of 14 lesions; this corresponded to CPN in 1 of 3 and 2 of 4 cases (Table 2; Fig. 3). Compared to baseline, ADC (P = 0.46) values did not differ at 1 or 3 months (Fig. 2). With response defined as an ADC increase ≥5% from baseline, 9 of 15 and 8 of 12 lesions were classified as responders at 1 and 3 months, respectively (Table 2), but without being able to predict pathological results. CPN as well as 50%-99% and <50% necrosis were observed in 5, 3, and 1 ADC responding lesions and 4, 1, and 1 ADC nonresponding lesions at 1 month (P = 0.47); at 3 months, it was 4, 2, and 2 ADC responding lesions and 2, 1, and 1 ADC nonresponding lesions (P = 0.73; Fig. 3). The subjective response assessment showed good results in predicting pathological results, particularly for one of the investigators (F.M.

The molecular mechanisms of CAR-mediated tumor promotion are not well understood but might be linked to repression of cell death and its interaction

with a growth arrest and DNA damage-inducible factor 45beta.175 PPARα ligands induce peroxisomal proliferation and development of HCC in rodents but not in humans176,177 (Supporting Table 7). In mice, stimulation of PPARα represses the microRNA (miRNA) let-7, which degrades the c-myc oncogene.178 This in turn induces oncogenic mir-17 miRNA cluster expression which PD98059 mw is critical for liver proliferation and tumorigenesis.179 Moreover, mouse PPARα induces the expression of gatekeeper genes involved in cell cycle progression.180 PXR plays a role in liver regeneration probably by way of modulating the required lipid accumulation in the proliferating hepatocytes in the early phases of restoration and potentially by way of signal transducer

and activator of transcription 3 (STAT3) modulation in the later phases.181 Also, LXR seems to be critically involved in order to provide the required cholesterol levels for regenerating hepatocytes.182 Recently, polymorphisms in the VDR have been associated with the occurrence of HCC in cirrhotic patients,183 linking VDR to cancer formation also in the liver. Finally, the role of estrogen receptors (which are key regulators of cholangiocyte proliferation) may deserve further studies.184 In summary, NRs

play a key role in the transcriptional control of several pivotal aspects of liver function. Understanding of NR biology is therefore 上海皓元 relevant for explaining find more the pathophysiology of a wide range of liver diseases. Moreover, NRs may represent valid therapeutic targets for these disorders. Specific targeting of individual NRs is an elegant and very effective way to treat diseases by readjusting deregulated NR-mediated pathways. This is most obvious for diseases (e.g., hypothyroidism, rickets) which clearly affect one of the classical endocrine nuclear hormone receptor (e.g., thyreoid receptor, VDR). The adoption of orphan NRs and the development of specific and selective agonists now has significantly extended the spectrum of diseases to the liver and associated/underlying metabolic disturbances (e.g., metabolic syndrome, insulin resistance), which can potentially be targeted. One of the most promising novel NR targets is FXR, which already has been shown to be successfully targeted in clinical phase trials in primary biliary cirrhosis. In addition, the FXR effects on lipid and glucose homeostasis make this NR also an ideal target for NAFLD and associated IR, which is currently being tested in clinical trials. A major future challenge will be to integrate the role of coactivators and corepressors into current pathogenetic and therapeutic concepts for liver disease.