67 Lately, considerable emphasis has been placed on preoperative

67 Lately, considerable emphasis has been placed on preoperative identification of a potentially involved circumferential surgical margin as a strong predictor of poor outcome after total mesorectal excision, and it has been suggested that MRI accurately predicts margin involvement.68,69 However, the few studies which claim to support this have significant methodological problems and further work, with improved study design, is needed before MRI is validated for this purpose.70 H 89 research buy As yet there is no evidence base for PET preoperative T and N staging of rectal cancer and the technique is not yet routinely used for this purpose.64,66 However, PET may assist in identifying systemic distant metastases when CT results are

equivocal.66 The various techniques that Selleck Ivacaftor have been applied to preoperative staging of rectal cancer have raised questions about the adequacy

of the existing TNM nomenclature for staging. It has therefore been suggested that each component of stage should be prefixed by an identifier for the source of information: “u” for ultrasound, “ct” for CT scan, “mr” for MRI scan, “p” for pathology, and “y” for staging following neoadjuvant therapy (and other more complex prefixes).71 Any move in this direction would be justifiable only if it leads to needed clarification in the transmission of staging results between practitioners and specialties, rather than further complicating an increasingly complex and unwieldy system. Despite enthusiasm in some quarters, the ability of EUS, CT, MRI and PET to preoperatively stage rectal cancer with high accuracy and consistency across a range of clinical environments has yet to be demonstrated. New technologies could lead to improvements but agreement about criteria for interpretation of images and issues of inter-observer reproducibility may remain highly problematic. The increasing use of neoadjuvant chemoradiotherapy has added to the complexity of staging. By convention, the postoperative staging of rectal carcinoma following neoadjuvant therapy reflects the extent of tumor present in the resected specimen and

does not give an indication of the spread of tumor prior to treatment. Grading systems have been devised to give an indication of response to neoadjuvant therapy,72 based on assessments of MCE公司 the extent of viable cancers cells and fibrosis. The prognostic significance of these measures remains to be determined. The staging of CRC is an evolving discipline in which the clinicopathological approach is now the accepted standard. The earlier focus of staging on predicting survival based on histopathological assessment of the operative specimen has broadened to encompass preoperative assessments by imaging and a range of potentially useful additional histological and molecular features. However, the strong association between traditional clinicopathological stage and patient survival has yet to be supplanted by any other prognostic indicators.

It has become the most common cause of chronic liver disease, and

It has become the most common cause of chronic liver disease, and yet there continues to be a lack of effective therapeutic options. This article reviews current concepts underlying the pathophysiological basis of nonalcoholic steatohepatitis from development of insulin resistance to the establishment of fibrosis. Then using a physiology-based approach, specific targeted therapeutics are reviewed along with their drawbacks. The evidence behind current therapies is based predominantly on small trials and, thus, no recommendations can be made until larger randomized trials are

conducted. “
“Hepatitis B virus (HBV) resistance to nucleoside/nucleotide analogs is frequent. Ultra-deep pyrosequencing (UDPS) is a powerful new tool that can detect minor viral variants and characterize complex quasispecies mixtures. We used UDPS SCH 900776 molecular weight to analyze the dynamics of adefovir-resistant HBV variants in patients with chronic HBV infection in whom adefovir resistance occurred during treatment. Amino acid substitutions known to confer resistance to adefovir were detected at baseline in most patients. The dynamics of adefovir-resistant variants were complex and differed among patients as a result of evolving differences in variant fitness.

UDPS analysis revealed successive selleck chemical waves of selection of HBV populations with single and multiple amino acid substitutions. Adefovir-resistant variants were partially inhibited by lamivudine, but remained fit in its presence. Conclusion: Substitutions conferring HBV resistance to nucleoside/nucleotide analogs exist before treatment, and that the dynamics of adefovir-resistant populations are much more complex and heterogeneous MCE than previously thought and involve thus far unknown amino acid substitutions. The UDPS-based approach described here is likely to have important implications for the assessment

of antiviral drug resistance in research and clinical practice. (Hepatology 2013;53:890–901) Approximately 240 million individuals worldwide are chronically infected with hepatitis B virus (HBV).[1] Chronic HBV infection is the leading cause of chronic liver disease and accounts for nearly 1 million deaths every year.[2-4] Chronic hepatitis B (CHB) can be treated with either pegylated interferon alpha or nucleoside/nucleotide analogs. The latter drugs act by directly inhibiting the enzymatic function of HBV reverse transcriptase, the enzyme responsible for viral replication. Five such drugs have been approved for HBV therapy, namely, three nucleoside analogs (lamivudine, telbivudine, and entecavir) and two nucleotide analogs administered as prodrugs (adefovir dipivoxil and tenofovir disoproxil fumarate). The vast majority of HBV-infected patients have an indication for therapy with nucleoside/nucleotide analogs.

For healthy volunteers, there was significantly less breath metha

For healthy volunteers, there was significantly less breath methane produced during the HFD (47 ± 29 ppm.14 h) compared with that during the LFD (109 ± 77 ppm.14 h; P = 0.043) see more (Fig. 4). In contrast, patients with IBS had no change in breath methane with the HFD (126 ± 153 ppm.14 h) compared with that on the LFD (86 ± 72 ppm.14 h; P = 0.280).

There was no significant difference in methane gas production between patients with IBS and healthy controls during either the LFD (P = 0.499) and HFD (P = 0.125) dietary periods. Since the effects of the diets on symptoms were similar at the end of the first and second days of the dietary periods, only day 2 results are shown. Symptom scores during the low and high FODMAPs diet for healthy subjects and patients with IBS were assessed according to a self-rating Likert

scale where 0 = no symptoms, 1 = slight, 2 = moderate, 3 = severe are shown in Table 3. In patients with IBS all symptoms were significantly worse with the HFD when considered individually (Table 3). In the healthy subjects, the only symptom to change significantly was an increase in the passage of flatus (Table 3). A composite IBS symptom score that included the most commonly reported IBS gastrointestinal symptoms (abdominal pain, bloating and wind) was selleck chemicals significantly higher for IBS patients during the HFD (median 6; range 2–9) than during the LFD (2; 0–7; P = 0.002). In healthy MCE公司 volunteers, the composite score was also higher during the HFD (3; 0–5 vs 1; 0–4; P = 0.014), but this was due to the increased

flatus passed. In the IBS group, upper gastrointestinal symptoms and lethargy increased during the HFD (Table 3). There was no association of the pattern of hydrogen and methane production with the induction of symptoms (data not shown). Luminal distension is a major stimulus for the induction of gastrointestinal symptoms associated with IBS. The predominant way that diet can potentially alter the volume of contents within the intestinal lumen is via intraluminal gas production. The present study has demonstrated that dietary manipulation of poorly absorbed short-chain carbohydrates (FODMAPs) can impact on the total amount of gastrointestinal gas production and the spectrum of gas produced (hydrogen vs methane) in healthy individuals and in hydrogen production in patients with IBS. It can induce gastrointestinal symptoms and systemic symptoms predominantly in those with IBS. The two test diets used were matched for all carbohydrate substrates except FODMAPs that potentially would be available for bacterial fermentation in the distal small and large intestine. Thus, contents of resistant starch and non-starch polysaccharide were similar, but the amount of oligosaccharides, fructose, lactose and polyols differed by approximately 40 g. Furthermore, all food consumed was provided to the participants and their adherence to the dietary protocol was high.

For healthy volunteers, there was significantly less breath metha

For healthy volunteers, there was significantly less breath methane produced during the HFD (47 ± 29 ppm.14 h) compared with that during the LFD (109 ± 77 ppm.14 h; P = 0.043) H 89 order (Fig. 4). In contrast, patients with IBS had no change in breath methane with the HFD (126 ± 153 ppm.14 h) compared with that on the LFD (86 ± 72 ppm.14 h; P = 0.280).

There was no significant difference in methane gas production between patients with IBS and healthy controls during either the LFD (P = 0.499) and HFD (P = 0.125) dietary periods. Since the effects of the diets on symptoms were similar at the end of the first and second days of the dietary periods, only day 2 results are shown. Symptom scores during the low and high FODMAPs diet for healthy subjects and patients with IBS were assessed according to a self-rating Likert

scale where 0 = no symptoms, 1 = slight, 2 = moderate, 3 = severe are shown in Table 3. In patients with IBS all symptoms were significantly worse with the HFD when considered individually (Table 3). In the healthy subjects, the only symptom to change significantly was an increase in the passage of flatus (Table 3). A composite IBS symptom score that included the most commonly reported IBS gastrointestinal symptoms (abdominal pain, bloating and wind) was selleckchem significantly higher for IBS patients during the HFD (median 6; range 2–9) than during the LFD (2; 0–7; P = 0.002). In healthy MCE公司 volunteers, the composite score was also higher during the HFD (3; 0–5 vs 1; 0–4; P = 0.014), but this was due to the increased

flatus passed. In the IBS group, upper gastrointestinal symptoms and lethargy increased during the HFD (Table 3). There was no association of the pattern of hydrogen and methane production with the induction of symptoms (data not shown). Luminal distension is a major stimulus for the induction of gastrointestinal symptoms associated with IBS. The predominant way that diet can potentially alter the volume of contents within the intestinal lumen is via intraluminal gas production. The present study has demonstrated that dietary manipulation of poorly absorbed short-chain carbohydrates (FODMAPs) can impact on the total amount of gastrointestinal gas production and the spectrum of gas produced (hydrogen vs methane) in healthy individuals and in hydrogen production in patients with IBS. It can induce gastrointestinal symptoms and systemic symptoms predominantly in those with IBS. The two test diets used were matched for all carbohydrate substrates except FODMAPs that potentially would be available for bacterial fermentation in the distal small and large intestine. Thus, contents of resistant starch and non-starch polysaccharide were similar, but the amount of oligosaccharides, fructose, lactose and polyols differed by approximately 40 g. Furthermore, all food consumed was provided to the participants and their adherence to the dietary protocol was high.

765% were diagnosied by ultrasound-guided peritoneal biopsy, whi

76.5% were diagnosied by ultrasound-guided peritoneal biopsy, which confirmed its main diagnostic methods; 79.0% were epithelial type; intraperitoneal chemotherapy was the main treatment method; and the average survival time was 1.1 years. Conclusion: PMM was closely related to asbestos exposure in this region, and women accounting for the majority. Ultrasound-guided peritoneal biopsy was the preferred diagnostic method and intraperitoneal chemotherapy was the main treatment method. These findings suggest the arrival of the incidence peak of PMM in this region. Key Word(s): 1. mesothelioma; 2. Asbestos; 3. biopsy; 4.

chemotherapy; Presenting Author: RUNWEI YAN Corresponding Author: RUNWEI YAN Affiliations: The First Affiliated Hospital of Nanchang University

Objective: Lindera strychnifolia (Sieb. and Zucc.) F. Villars (Lauraceae) is a well-known herb in traditional Chinese medicine, has been used in the treatment of check details stomach and renal diseases, neuralgia, rheumatism, hyperkinesias. The aim of this study is to determine cytotoxic activity and mechanism of induction of HepG2 cell death of Lindera strychnifolia leaf essential oil. Methods: Cytotoxicities of leaf oil on eight human carcinoma cells (Eca-109, HepG2, HT29, MDA-MB-231, PC-3, see more SGC7901, SW1990 and U2-OS) and a normal cell HL-7702 were examined using MTT assay. Apoptotic effect of leaf oil on HepG2 was investigated using Hoechst 33258 staining, agarose gel electrophoresis and flow cytometer technique. Besides, cytotoxicities of four compounds from the essential oil were further investigated. Results: Leaf essential oil exhibited significant cytotoxicity against all the cells tested, and had potential cancerous cell selectivity. The lowest IC50 of 22.68 ± 1.19 μg/ml was measured for HepG2. The anticancer mechanism of leaf oil on HepG2 involved induction of apoptosis. Conclusion: Lindera strychnifolia leaf essential oil shows significant cytotoxicity and potential cancerous cell selectivity suggests that it could be a potential medicinal resource in cancer therapy. Key Word(s): 1. L. strychnifolia; 2. cytotoxic effect;

3. apoptotic effect; 4. essential oil; MCE Presenting Author: YAN PAN Additional Authors: NA LIU, LI XU, XIAOYIN ZHANG, XIN WANG Corresponding Author: YAN PAN Affiliations: Xijing Hospital of Digestive Diseases Objective: The aim of this study was to explore the effect of education background and family income of the patients of clinical trials into the group and their adherence. Methods: A total of 73 patients with gastrointestinal cancer, who were participated in clinical trials at the Xijing Hospital of Digestive Diseases were enrolled in this study. These patients were divided into the following groups according to the education background. Group I: primary school to junior high school (30 patients), Group II: junior high school to college graduate (43 patients).

765% were diagnosied by ultrasound-guided peritoneal biopsy, whi

76.5% were diagnosied by ultrasound-guided peritoneal biopsy, which confirmed its main diagnostic methods; 79.0% were epithelial type; intraperitoneal chemotherapy was the main treatment method; and the average survival time was 1.1 years. Conclusion: PMM was closely related to asbestos exposure in this region, and women accounting for the majority. Ultrasound-guided peritoneal biopsy was the preferred diagnostic method and intraperitoneal chemotherapy was the main treatment method. These findings suggest the arrival of the incidence peak of PMM in this region. Key Word(s): 1. mesothelioma; 2. Asbestos; 3. biopsy; 4.

chemotherapy; Presenting Author: RUNWEI YAN Corresponding Author: RUNWEI YAN Affiliations: The First Affiliated Hospital of Nanchang University

Objective: Lindera strychnifolia (Sieb. and Zucc.) F. Villars (Lauraceae) is a well-known herb in traditional Chinese medicine, has been used in the treatment of check details stomach and renal diseases, neuralgia, rheumatism, hyperkinesias. The aim of this study is to determine cytotoxic activity and mechanism of induction of HepG2 cell death of Lindera strychnifolia leaf essential oil. Methods: Cytotoxicities of leaf oil on eight human carcinoma cells (Eca-109, HepG2, HT29, MDA-MB-231, PC-3, PCI-32765 clinical trial SGC7901, SW1990 and U2-OS) and a normal cell HL-7702 were examined using MTT assay. Apoptotic effect of leaf oil on HepG2 was investigated using Hoechst 33258 staining, agarose gel electrophoresis and flow cytometer technique. Besides, cytotoxicities of four compounds from the essential oil were further investigated. Results: Leaf essential oil exhibited significant cytotoxicity against all the cells tested, and had potential cancerous cell selectivity. The lowest IC50 of 22.68 ± 1.19 μg/ml was measured for HepG2. The anticancer mechanism of leaf oil on HepG2 involved induction of apoptosis. Conclusion: Lindera strychnifolia leaf essential oil shows significant cytotoxicity and potential cancerous cell selectivity suggests that it could be a potential medicinal resource in cancer therapy. Key Word(s): 1. L. strychnifolia; 2. cytotoxic effect;

3. apoptotic effect; 4. essential oil; MCE Presenting Author: YAN PAN Additional Authors: NA LIU, LI XU, XIAOYIN ZHANG, XIN WANG Corresponding Author: YAN PAN Affiliations: Xijing Hospital of Digestive Diseases Objective: The aim of this study was to explore the effect of education background and family income of the patients of clinical trials into the group and their adherence. Methods: A total of 73 patients with gastrointestinal cancer, who were participated in clinical trials at the Xijing Hospital of Digestive Diseases were enrolled in this study. These patients were divided into the following groups according to the education background. Group I: primary school to junior high school (30 patients), Group II: junior high school to college graduate (43 patients).

O estimulador

do gânglio esfenopalatino é aprovado na Eur

O estimulador

do gânglio esfenopalatino é aprovado na Europa para uso em cefaleia em salvas crônica. Estudos sobre estimulação não invasiva do nervo vago, uso do estimulador do gânglio esfenopalatino e estimulação do nervo occipital serão realizados nos EUA em 2014. Até o momento nenhum desses dispositivos para neuromodulação foi aprovação pelo FDA para uso nos EUA. Para encontrar mais recursos visite The American Cobimetinib Migraine Foundation (http://kaywa.me/ir2eb) “
“The practice of headache medicine is challenging, and excluding secondary causes of headaches is essential for proper diagnosis and treatment. The evaluation of secondary headaches often leads to investigations involving organ systems other than the nervous system. As such, headache, which is typically thought to be neurologic in origin, can be a manifestation of cardiac pathology in the form of cardiac cephalalgia. Conversely, chest pain, which is typically thought selleckchem to be cardiac in origin, could be a manifestation of a neurologic disease process in the form of atypical migraine aura. In the presented cases, we demonstrate headaches that involve cardiac and neurologic pathology with atypical presentations. “
“Though thyroid growths are considered to be a frequent cause of Horner’s

syndrome, concurrent headache attacks are not commonly seen. A 63-year-old woman presented with severe, daily occurring, unilateral headache attacks with ipsilateral Horner’s

syndrome. Magnetic resonance imaging arteriography showed a multinodular goiter displacing the left common carotid artery. This case exemplifies the combination of headache attacks and Horner’s syndrome due to mechanical pressure of an enlarged thyroid, mimicking the symptoms both of carotid dissection as well as trigeminal autonomic cephalgias like paroxysmal hemicrania. “
“The International Classification of Headache medchemexpress Disorders, 3rd Edition (ICHD-3) beta version defines migrainous infarction as 1 or more otherwise typical aura symptoms that persist beyond 1 hour with neuroimaging confirmation of an ischemic infarction in the affected territory.[1] Here we describe a woman with migraine with brainstem aura, who experienced acute-onset left sensorimotor deficits in addition to her typical aura symptoms in the midst of a prolonged, but otherwise typical attack. Magnetic resonance imaging (MRI) of the brain revealed a pontine lesion consistent with an ischemic stroke. Our case illustrates potential limitations of the ICHD-3 beta definition of migrainous infarction. Our patient developed episodic headaches that fulfilled ICHD-3 beta criteria for episodic migraine without aura in her adolescence.[1] At the age of 30, she began to experience episodes of transient neurological symptoms antecedent to her typical headache attacks.

No concomitant medications (prescription, over-the-counter, or he

No concomitant medications (prescription, over-the-counter, or herbal) were permitted to be administered during the study, unless they were prescribed by the investigator for treatment of specific clinical events or were approved by the medical monitor prior to dosing. The study was approved by the Institutional Review Boards of all study centers and conducted in accordance with Good Clinical Practice, as defined by the International Conference on Harmonization, in accordance selleck compound with the ethical principles underlying European Union Directive 2001/20/EC and the United States Code of Federal Regulations, Title 21, Part 50 (21CFR50), and in

accordance with the ethical principles that have their origin in the Declaration of Helsinki. Informed written consent was obtained from all patients. Patients were randomly assigned to receive BMS-790052 or placebo according to a computer-generated randomization scheme prepared by Bristol-Myers Squibb. An Interactive Voice Response System was used to assign a unique subject number and a blinded container number, which was provided to the blinded study staff who supervised and recorded the drug administration. The sample size was based on the primary endpoint of the study, defined as the change in log10 HCV RNA from baseline to Erastin mw day 7.

A mean decrease of at least 1.5 log10 HCV RNA within one dose panel would suggest that BMS-790052 was sufficiently active to proceed to late phase development. If BMS-790052 had no effect, administration of drug to four patients within a dose panel would yield a probability of 0.01 to observe a mean decrease in log10 HCV RNA of more than 1.5. If the true mean decrease was 2.0, the probability of observing a mean decrease in log10 HCV RNA of more than 1.5 would be 0.78. These calculations are based on the assumption

that log10 HCV RNA is normally distributed, with a standard deviation for the change of 1.3. Eligible patients for this study were men and women, ages 18-60 years inclusive, with a body mass index of 18-35 kg/m2, who were chronically infected (longer than 6 months) with HCV genotype 1, and who were treatment-naive 上海皓元 to interferon and RBV. Additional inclusion criteria were: plasma HCV RNA ≥100,000 IU/mL; documented FibroTest score of ≤0.72 and APRI ≤2, or the absence of cirrhosis based on liver biopsy within 12 months; women of childbearing potential were not to be nursing or pregnant and had to be willing to agree to use double barrier contraception for at least 1 month before dosing, during dosing, and at least 12 weeks after the last dose of study medication. The main exclusion criteria were: patients with prior documented cirrhosis on liver biopsy; previous exposure to a NS5A replication cofactor inhibitor; coinfection with human immunodeficiency virus; coinfection with hepatitis B virus.

No concomitant medications (prescription, over-the-counter, or he

No concomitant medications (prescription, over-the-counter, or herbal) were permitted to be administered during the study, unless they were prescribed by the investigator for treatment of specific clinical events or were approved by the medical monitor prior to dosing. The study was approved by the Institutional Review Boards of all study centers and conducted in accordance with Good Clinical Practice, as defined by the International Conference on Harmonization, in accordance LBH589 clinical trial with the ethical principles underlying European Union Directive 2001/20/EC and the United States Code of Federal Regulations, Title 21, Part 50 (21CFR50), and in

accordance with the ethical principles that have their origin in the Declaration of Helsinki. Informed written consent was obtained from all patients. Patients were randomly assigned to receive BMS-790052 or placebo according to a computer-generated randomization scheme prepared by Bristol-Myers Squibb. An Interactive Voice Response System was used to assign a unique subject number and a blinded container number, which was provided to the blinded study staff who supervised and recorded the drug administration. The sample size was based on the primary endpoint of the study, defined as the change in log10 HCV RNA from baseline to PD0325901 mouse day 7.

A mean decrease of at least 1.5 log10 HCV RNA within one dose panel would suggest that BMS-790052 was sufficiently active to proceed to late phase development. If BMS-790052 had no effect, administration of drug to four patients within a dose panel would yield a probability of 0.01 to observe a mean decrease in log10 HCV RNA of more than 1.5. If the true mean decrease was 2.0, the probability of observing a mean decrease in log10 HCV RNA of more than 1.5 would be 0.78. These calculations are based on the assumption

that log10 HCV RNA is normally distributed, with a standard deviation for the change of 1.3. Eligible patients for this study were men and women, ages 18-60 years inclusive, with a body mass index of 18-35 kg/m2, who were chronically infected (longer than 6 months) with HCV genotype 1, and who were treatment-naive 上海皓元 to interferon and RBV. Additional inclusion criteria were: plasma HCV RNA ≥100,000 IU/mL; documented FibroTest score of ≤0.72 and APRI ≤2, or the absence of cirrhosis based on liver biopsy within 12 months; women of childbearing potential were not to be nursing or pregnant and had to be willing to agree to use double barrier contraception for at least 1 month before dosing, during dosing, and at least 12 weeks after the last dose of study medication. The main exclusion criteria were: patients with prior documented cirrhosis on liver biopsy; previous exposure to a NS5A replication cofactor inhibitor; coinfection with human immunodeficiency virus; coinfection with hepatitis B virus.

As shown in Fig 2C, C/EBPα activated the reporter gene through t

As shown in Fig. 2C, C/EBPα activated the reporter gene through the E2 fragment. Next, we performed mutational analyses on predicted HNF binding sites. Because the multiple putative C/EBPα target sites were arranged in a tandem array, we did not perform mutation analysis on these sites. As shown in Fig. 2D, mutagenesis of certain conserved PD 332991 sites (F4A-3, F3B-1, and F1A-3) abolished the effects of HNFs on the reporter, but mutations of all nonconserved sites made no difference. Remarkably, the F4A-3 site was a crucial site, because its mutation completely abolished the miR-122 promoter function. The F3B-1 and F1A-3 sites overlapped (Table 1), and mutations in these sites eliminated the effects

of both HNF1α and HNF3β. These data

demonstrate that the HNFs could directly bind to the miR-122 promoter. This conclusion was further confirmed by way of chromatin immunoprecipitation assay. As shown in Fig. 2E, the three HNFs directly bind to the miR-122 promoter in Huh7 cells. To test whether the LETFs could up-regulate miR-122 expression in HCC cells, we performed overexpression studies. As shown in Fig. 2F, cells transfected with LETF-expressing vectors display an obvious up-regulation of miR-122, I-BET-762 cost especially for C/EBPα. Moreover, this finding is consistently observed in the three cell lines used. Together, these results show that C/EBPα, HNF1α, HNF3β, and HNF4α are involved in the transcriptional regulation of miR-122, which also suggests that miR-122 functions as an effector of these LETFs during liver development. Cellular proliferation and differentiation are the two most important processes for organ development.23 Numerous studies have established the pivotal roles of LETFs in the regulation of both processes during liver development.17-19 To search for the functional targets of miR-122, we primarily focused on candidate target genes with the potential to suppress differentiation and/or promote proliferation, which are contrary to the roles of LETFs. Eleven

candidate targets were arbitrarily selected from the results predicted by Targetscan 4.2 for further confirmation (Table 2). In addition, CCNG1 and BCL2L2, two known targets of miR-122, were 上海皓元 employed as positive controls.16, 24 The 3′-UTR segments of each target were synthesized and subcloned downstream of the Renilla luciferase in the psiCHECK-2 dual luciferase reporter vector (Fig. 3A), and reporter assays were performed as indicated. Surprisingly, as shown in Fig. 3B, 11 reporters were significantly repressed by miR-122 to different degrees (30%-70% reduction), including the two known targets. MSN (moesin) and serum response factor (SRF) were not significant in this group. These data indicate that most candidate genes could be directly repressed by miR-122. To further confirm this hypothesis, we performed mutational analyses on each predicted site.