Effects of niacin on apo A1 and B levels: a systematic review and meta-analysis of randomised controlled trials.

Niacin has been investigated for its potential impact on lipid metabolism and cardiovascular health. This meta-analysis aims to systematically evaluate the effects of niacin interventions on apo A1 and apo B levels, key regulators of lipoprotein metabolism and markers of cardiovascular risk. A comprehensive search of the literature was performed on five databases of PubMed, Scopus, Web of Science, Embase and Cochrane library, from inception up to 15 July 2023. This search identified 1452 publications, from which twelve randomised controlled trials met the inclusion criteria. The intervention dosages ranged from 500 to 3000 mg/d, and the study durations spanned from 6 to 102·8 weeks. The niacin intervention demonstrated a significant reduction in apo B levels (weighted mean differences (WMD): -24·37 mg/dl, P = 0·01). Subgroup analyses indicated that intervention duration played a role, with trials of ≤ 16 weeks showing a greater reduction in apo B. Regarding apo A1, niacin significantly increased its levels (WMD: 8·23 mg/dl, P < 0·001). Subgroup analyses revealed that the beneficial effects of niacin on apo A1 were observed at a dosage of > 1500 mg/d (P < 0·001), and extended-release niacin was more effective compared with other forms (P < 0·001). According to the Begg's regression test, no publication bias was observed in this systematic review and meta-analysis. This meta-analysis highlights niacin's potential role in improving lipid profiles and cardiovascular health. Further well-designed clinical trials are needed to elucidate and confirm optimal dosages and durations of niacin interventions for influencing apo A1 and B.

ApoA1/HDL-C ratio as a predictor for coronary artery disease in patients with type 2 diabetes: a matched case-control study.

INTRODUCTION: This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease (CAD) in patients with type 2 diabetes (T2D). METHODS: This was a matched case-control study of 482 patients with T2D in two groups of CAD and (n = 241) non-CAD (n = 241). The patients were classified into four quartiles according to the ApoA1/HDL-C ratio, and multivariate logistic regression analysis was performed to assess the relationship between ApoA1/HDL-C and CAD. ROC analysis was also conducted. RESULTS: This study showed that the ApoA1/HDL-C ratio has an independent association with CAD in individuals with T2D. The CAD group exhibited a significantly higher ApoA1/HDL-C ratio than those without CAD (p-value = 0.004). Moreover, the risk of CAD increased significantly across the ApoA1/HDL-C ratio quartiles, with the highest odds in the fourth quartile. The second quartile showed an odds ratio (OR) of 2.03 (p-value = 0.048) compared to the first. Moving to the third quartile, the OR increased to 2.23 (p-value = 0.023). The highest OR was noted in the fourth, reaching 3.41 (p-value = 0.001). Employing a cut-off value of 2.66 and an area under the curve (AUC) of 0.885, the ApoA1/HDL-C ratio predicts CAD among patients with T2D with a sensitivity of 75% and a specificity of 91% (p-value < 0.001). CONCLUSION: The current study revealed an independent association between ApoA1/HDL-C ratio and CAD in patients with T2D. This ratio can be a promising tool for predicting CAD during the follow-up of patients with T2D, aiding in identifying those at higher risk for CAD.

An Electrodeposited MXene-Ti3C2Tx Nanosheets Functionalized by Task-Specific Ionic Liquid for Simultaneous and Multiplexed Detection of Bladder Cancer Biomarkers.

Controlled deposition of 2D multilayered nanomaterials onto different electrodes to design a highly sensitive biosensing platform utilizing their active inherent electrochemistry is extremely challenging. Herein, a green, facile, and cost-effective one-pot deposition mechanism of 2D MXene-Ti3C2Tx nanosheets (MXNSs) onto conductive electrodes within few minutes via electroplating (termed electroMXenition) is reported for the first time. The redox reaction in the colloidal MXNS solution under the effect of a constant applied potential generates an electric field, which drives the nanoparticles toward a specific electrode interface such that they are cathodically electroplated. A task-specific ionic liquid, that is, 4-amino-1-(4-formyl-benzyl) pyridinium bromide (AFBPB), is exploited as a multiplex host arena for the substantial immobilization of MXNSs and covalent binding of antibodies. A miniaturized, single-masked gold dual interdigitated microelectrode (DIDµE) is microfabricated and presented by investigating the benefit of AFBPB coated on MXNSs. The resulting MXNSs-AFBPB-film-modified DIDµE biosensor exhibited a 7× higher redox current than bare electrodes owing to the uniform deposition. Using Apo-A1 and NMP 22 as model bladder cancer analytes, this newly developed dual immunosensor demonstrated precise and large linear ranges over five orders of significance with limit of detection values as low as 0.3 and 0.7 pg mL-1, respectively.

The effects of isolated soy protein, isolated soy isoflavones and soy protein containing isoflavones on serum lipids in postmenopausal women: A systematic review and meta-analysis.

Background: Many randomized controlled trials (RCTs) have assessed the effects of soy products on serum lipids. However, the responsible soy components and the magnitude of effects in healthy or hypercholesterolemic postmenopausal women are unclear. This review assessed the quality of these RCTs and estimated the effects of isolated soy protein, isolated soy isoflavones and soy protein containing isoflavones on total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), Apolipoprotein (Apo) A-1 and Apo B among postmenopausal women.Design: Forty-six eligible randomized controlled trials published up to 20 May 2019 were identified from the PubMed, Web of Science and Scopus databases. Weighted mean effect sizes were calculated for net changes in serum lipid concentrations by using random-effect models. Specific subgroup analyses were performed to identify the effect of covariates on serum lipid changes.Results: Soy consumption was associated with significant decrease in TG (mean differences (MD): -5.04 mg/dl; 95% CI: -9.95, -0.13; P = 0.044), TC (MD: -3.02 mg/dl; 95% CI: -5.56, -0.47; P = 0.02), LDL-C (MD: -3.27 mg/dl; 95% CI: -6.01, -0.53; P = 0.019) and HDL-C (MD: -2.28 mg/dl; 95% CI: -4.27, -0.29; P = 0.025). The reduction in LDL-C, TG and HDL were larger in subjects consuming isolated soy protein than isolated soy isoflavones. There was a significant decrease in serum TG and HDL levels with dosages of >25 grams per day soy protein rather than lower dosages of soy protein. The reductions in Apo A-1 were significantly larger in hypercholesterolemic subjects than in healthy subjects.Conclusions: Isolated soy protein significantly reduced serum TG, TC, LDL-C, HDL-C and Apo-B levels in postmenopausal women. Isolated soy isoflavones had a significant lowering effect on serum TC and Apo B levels. Soy protein containing isoflavones significantly reduced TG, TC, LDL-C and Apo B levels. Therefore, hyperlipidemia risk reduction with soy products is not uniform and strongly depends on the protein and isoflavone content of soy products, duration and dosage of consumption.

Apolipoprotein A1 distribution pattern in the human Achilles tendon.

Metabolic factors such as cholesterol appear to play an important role in the development of Achilles tendinopathy. There is, however, no morphologic proof explaining the link between high cholesterol and tendinopathy. As apolipoprotein A1 (Apo-A1) is essential for reverse cholesterol transport, it may be related to cholesterol overload in tendon. Nothing is known about Apo-A1 expression in tendon tissue. We examined the distribution of Apo-A1 protein in biopsies from normal and tendinopathy-affected human Achilles tendons, and APOA1 mRNA production from cultured human hamstring tenocytes. Specific immunoreactions for Apo-A1 were detected. The tenocytes showed specific Apo-A1 immunoreactions. These reactions were usually distinct in the tendinopathy specimens. While the tendinopathy specimens often showed granular/small deposit reactions, the slender tenocytes of control specimens did not show this pattern. The magnitude of Apo-A1 immunoreactivity was especially marked in the tendinopathy specimens, as there is a high number of tenocytes. Reactions were also seen in the walls of blood vessels located within the tendon tissue proper of both the normal and tendinopathy tendons and within the peritendinous/fatty tissue of the tendinopathy tendons. The reactions were predominantly in the form of deposit reactions within the smooth muscle layer of the vessel walls. Cultured hamstring tenocytes produced APOA1 mRNA. We demonstrated the presence of Apo-A1 in human tendon tissue. This suggests there may be a link between Achilles tendinopathy and cholesterol metabolism. We hypothesize that Apo-A1 may be important for tenocyte and blood vessel function within tendons.

Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes.

OBJECTIVES: Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. METHODS: Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of upregulated protein were detected by matrix-assisted laser desorption-ionisation time-of-flight MALDI-TOF mass spectrometry and analysed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. RESULTS: Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. CONCLUSION: Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis.

Adult lipids associated with early life growth in traditional Melanesian societies undergoing rapid modernization: a longitudinal study of the mid-20th century.

Both poor fetal development and accelerated post-natal growth have been linked to adult dyslipidemias in many studies conducted in developed societies. It is not known, however, whether these relationships only characterize populations with typical Western diets or if they also may develop in groups at the early stages of a dietary transition. Our longitudinal study of traditional rural populations in the Southwest Pacific during a period of extremely rapid modernization in diet and life-styles shows a nascent association between child growth retardation, subsequent growth acceleration, and adult lipid values in spite of a continuing prevalence of very low lipid levels. However, our results do not entirely conform to results from populations with "modern" diets. Outcome (i.e., young adult) cholesterol and triglyceride levels are more consistently related to initial measures of body fat and growth in body fat measures than with stature, while outcome apo A-1 is more consistently related to initial stature or stature growth than to measures of body fat. We suggest this may reflect a pattern characteristic of the initial stages of "modernization" associated with dietary change, with stronger and more pervasive relationships emerging only later as populations complete the dietary transition.

Relationship between serum levels of fetuin-A with apo-A1, apo-B100, body composition and insulin resistance in patients with type 2 diabetes.

BACKGROUND: Some results exist on fetuin-A as marker for vascular disease in type 2diabetes. We examined the relationship between serum fetuin-A with some factors, in patients with type 2 diabetes mellitus (T2DM). METHODS: From October 2012 to June 2013, a total of 131 T2DM patients were recruited and evaluated for various parameters including HOMA-IR, Apo-A1, Apo-B100, body fat percentage and waist circumference. Serum fetuin-A levels were measured by enzyme-linkedimmunosorbent assay (ELISA), and Serum glucose with a Cobas MIRA analyzer by enzymatic method. Apo-B100 and apo-A1 were measured by immunoturbidimetry with a Cobas MIRA analyzer. HOMA-IR was calculated by the following formula: [fasting insulin (uIU/mL) × fasting blood glucose (mmol/L)]/22.5. RESULTS: The mean levels of HOMA-IR were significantly increased progressively across fetuin-A tertiles (p for trend=0.04) in women but not men. Fetuin-A had just a significant positive correlation with Apo- A1(r=0.22, p=0.02). CONCLUSION: This present study showed that levels of serum fetuin-A are significantly associated with insulin resistance in women with T2DM.

Repeat antenatal steroid exposure and later blood pressure, arterial stiffness, and metabolic profile.

OBJECTIVE: To determine the relationship between repeat courses of antenatal corticosteroids (ACS) and risk factors for cardiovascular disease in adolescents and young adults. STUDY DESIGN: We assessed body mass index, blood pressure, arterial stiffness, blood lipids, and insulin resistance (IR) in a Swedish population-based cohort (n = 100) at a median age of 18 (range 14-26) years. Fifty-eight subjects (36 males) had been exposed to 2-9 weekly courses of antenatal betamethasone and 42 (23 males) were unexposed subjects matched for age, sex, and gestational age (GA). RESULTS: There were no significant differences between the groups regarding body mass index, systolic or diastolic blood pressures, arterial stiffness measured by augmentation index, blood lipids, IR, or morning cortisol levels either in simple regression or in multivariable models. However, more subjects with elevated augmentation index had been exposed to repeat courses of ACS (n = 7) compared with unexposed subjects (n =1, P = .06), and glucose, insulin, and IR correlated inversely to GA at start of ACS (P < .01). CONCLUSIONS: Repeat courses of ACS did not correlate to adverse cardiovascular risk profile in adolescence and young adulthood, but long-standing effects on the arterial tree and glucose metabolism, the latter dependent on GA at ACS exposure, cannot be excluded. These observations have clinical implications for the ongoing discussion on short-term benefits and long-term safety of repeat ACS treatment.

Macadamia nut effects on cardiometabolic risk factors: a randomised trial.

We sought to examine the effects of daily consumption of macadamia nuts on body weight and composition, plasma lipids and glycaemic parameters in a free-living environment in overweight and obese adults at elevated cardiometabolic risk. Utilising a randomised cross-over design, thirty-five adults with abdominal obesity consumed their usual diet plus macadamia nuts (~15 % of daily calories) for 8 weeks (intervention) and their usual diet without nuts for 8 weeks (control), with a 2-week washout. Body composition was determined by bioelectrical impedance; dietary intake was assessed with 24-h dietary recalls. Consumption of macadamia nuts led to increased total fat and MUFA intake while SFA intake was unaltered. With mixed model regression analysis, no significant changes in mean weight, BMI, waist circumference, percent body fat or glycaemic parameters, and non-significant reductions in plasma total cholesterol of 2⋅1 % (-4⋅3 mg/dl; 95 % CI -14⋅8, 6⋅1) and low-density lipoprotein (LDL-C) of 4 % (-4⋅7 mg/dl; 95 % CI -14⋅3, 4⋅8) were observed. Cholesterol-lowering effects were modified by adiposity: greater lipid lowering occurred in those with overweight v. obesity, and in those with less than the median percent body fat. Daily consumption of macadamia nuts does not lead to gains in weight or body fat under free-living conditions in overweight or obese adults; non-significant cholesterol lowering occurred without altering saturated fat intake of similar magnitude to cholesterol lowering seen with other nuts. Clinical Trial Registry Number and Website: NCT03801837 https://clinicaltrials.gov/ct2/show/NCT03801837?term = macadamia + nut&draw = 2&rank = 1.

Pathways and Mechanisms of Cellular Cholesterol Efflux-Insight From Imaging.

Cholesterol is an essential molecule in cellular membranes, but too much cholesterol can be toxic. Therefore, mammalian cells have developed complex mechanisms to remove excess cholesterol. In this review article, we discuss what is known about such efflux pathways including a discussion of reverse cholesterol transport and formation of high-density lipoprotein, the function of ABC transporters and other sterol efflux proteins, and we highlight their role in human diseases. Attention is paid to the biophysical principles governing efflux of sterols from cells. We also discuss recent evidence for cholesterol efflux by the release of exosomes, microvesicles, and migrasomes. The role of the endo-lysosomal network, lipophagy, and selected lysosomal transporters, such as Niemann Pick type C proteins in cholesterol export from cells is elucidated. Since oxysterols are important regulators of cellular cholesterol efflux, their formation, trafficking, and secretion are described briefly. In addition to discussing results obtained with traditional biochemical methods, focus is on studies that use established and novel bioimaging approaches to obtain insight into cholesterol efflux pathways, including fluorescence and electron microscopy, atomic force microscopy, X-ray tomography as well as mass spectrometry imaging.

Protective and therapeutic potentials of HDL and ApoA1 in COVID-19 elderly and chronic illness patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease-2019 (COVID-19). Elderly subjects, obese, and patients with chronic illnesses, are the most affected group. HDL has pleiotropic physiological functions that are affected with alteration(s) in its structure. Main text: Inflammation whether septic, immune, or other affects HDL structure and function. COVID-19 is associated with systemic immune-inflammation due to cytokine surge. Viral interaction with erythrocytes and hemoglobin-related compounds (may cause anemia and hypoxia) and other factors may affect HDL function. Trials have been conducted to resume HDL functions using peptide preparation, nutritional, and herbal elements. Conclusions: In this review article, I'll discuss the use of reconstituted HDL (rHDL), Apo-A1 mimetic peptide D-4F, ω-3 polyunsaturated fatty acids, and the powdered roots and/or extract of Saussurea lappa (costus) to avoid comorbidity and mortality of COVID-19 in patients with chronic illness or elderly-age mortality.

D4F prophylaxis enables redox and energy homeostasis while preventing inflammation during hypoxia exposure.

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.

Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes.

Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) is characterized by asymptomatic, non-progressive and fasting hyperglycemia, albeit not without phenotypic variability. We used next generation sequencing (NGS) to screen for 34 MODY genes in a non-obese person with familial young-onset diabetes followed by screening in 24 family members within three generations with varying presentations of young-onset diabetes and sensorineural hearing loss. The index patient was found to carry a paternally-inherited heterozygous missense variant (c.716 A>G) of GCK in exon 7 with amino acid change (Q239R). This variant was associated with phenotypic heterogeneity ranging from normal glucose tolerance to diabetes with complications amongst the siblings which might be modified by obesity and chronic hepatitis B infection. Two paternally-inherited variants of SLC29A3 encoding a nucleoside transporter protein and Apo-A1 genes also co-segregated with glucose and lipid traits. Co-occurrence of diabetes and deafness in maternal aunts led to discovery of WFS1 (Wolfram syndrome type 1) as a cause of non-syndromic deafness in multiple members of the maternal pedigree. Our findings highlight the complex causes of familial young-onset diabetes and the need of a multidisciplinary approach to interpret the clinical relevance of discoveries made by NGS in this era of genomic medicine.

Evaluation of circulating miR-122, miR-30c and miR-33a levels and their association with lipids, lipoproteins in postprandial lipemia.

AIMS: Postprandial lipemia is characterized by an increase in triglyceride-rich lipoproteins after fatty meals. MicroRNAs (miRs) play important roles in lipid and lipoprotein metabolism. The aim of this study was to determine relationship between levels of plasma miR expression and lipoprotein metabolism-related proteins in subjects with normal (NPR) and high postprandial response (HPR) in postprandial period. MATERIALS AND METHODS: The oral fat tolerance test was applied to 22 individuals with NPR and 22 with HPR. KEY FINDINGS: Increased expressions of miR-122 and miR-33a and miR-122/30c ratio and decreased miR-30c expression were observed in fasting and postprandial period of HPR compared with NPR. ROC curve analysis showed that miR-122/30c ratio is a good biomarker for postprandial lipemia (AUC: 0.97, p < 0.001). Levels of TG, MTTP, and Apo B-48 and chylomicron (CM) particle size were significantly higher in HPR than in NPR (p < 0.05). The miR-122/30c ratio at 2 h was positively correlated with CM particle size, and with TG, MTTP and Apo B-48 levels at 4th hour. miR-33a expression decreased in HPR and was negatively correlated with ABCA1 and Apo A-1 levels at 4th hour of the postprandial period in both groups. SIGNIFICANCE: Increased miR-122 and decreased miR-30c expression levels in HPR may play critical roles in elevated or prolonged postprandial lipemia. The miR122/30c ratio exhibited good association with MTTP, Apo B-48 and TG levels, and with CM particle size, and may be a reliable marker for evaluating postprandial lipemia. miR-33a may also play a key role in decreased HDL-C in postprandial lipemia.

Effect of sumac (Rhus Coriaria) on blood lipids: A systematic review and meta-analysis.

Cardiovascular diseases (CVD) are the prominent cause of mortality worldwide. Hypercholesterolemia is a chief risk factor for the progress of atherosclerotic vascular disease. Complementary and alternative medicine (CAM) such as herbal interventions has received much attention in literature. Rhus Coriaria (RC) with the general name Sumac is a medicinal spice, especially in Middle Eastern countries which is well known as an anti-lipid spice. This study aimed to summarize the existing findings regarding the effect of RC on the lipid profile. In this review randomized controlled trials (RCTs) assessing the effect of RC on blood lipids were included. Electronic searches using the MeSH terms were conducted in the following databases: Medline, Embase, Scopus, Web of Science and The Cochrane Library. The effect of RC on serum lipid concentration were measured as standardized mean difference (SMD) and 95% confidence intervals (CI) by the random-effects model. The initial search extracted 119 potentially relevant articles. After studying these publications, 4 were potentially eligible and retrieved in full text (four RCTs). Based on the results of the systematic review, RC has positive effects on different indices of the lipid profile including increasing Apo A-I and HDL; decreasing Apo B, Apo B/ Apo A1 ratio, total cholesterol, LDL and triglyceride. However the meta-analysis conducted on three studies on total cholesterol, HDL, LDL and triglyceride individually did not show any significant difference between intervention and control groups. No definite conclusion could be made on the effect of RC on serum blood lipids due to lack of sufficient clinical trials and variable inconsistency. Future trials with desirable designs that would eliminate the limitations in the current evidence are needed before conclusive claims can be made about the effect of RC on the lipid profile.

Electrochemical synthesis of silver nanoclusters on electrochemiluminescent resonance energy transfer amplification platform for Apo-A1 detection.

Herein, a novel electrochemiluminescence resonance energy transfer (ERET) strategy between in situ electrogenerated silver nanoclusters (AgNCs) as the donor and Ru(bpy)2(5-NH2-1,10-phen)Cl2 (Ru(II)) as the acceptor was reported, which was applied for the construction of a ultrasensitive immunosensor for the determination of apolipoprotein-A1 (Apo-A1). Notably, the Ag NCs were in suit electro-reducted on glassy carbon electrode (GCE) based on a simple, fast and controllable electrochemical technique, which acted as not only biocompatible ECL emitters, but also protein immobilization platform via Ag-N or Ag-S bond. Subsequently, the acceptor probe was constructed by modifying Ru(II) and secondary antibody on the nanocarriers of carboxyl-functionalized MWCNTs. Based on the sandwiched immunoassay method, the ECL signals declining at 449nm (Ag NCs) and the increasing at 650nm (Ru(II)) both reflect the amount of Apo-A1. By measuring the ratio of ECL650nm/ECL449nm, we could accurately quantify the concentration of Apo-A1 in range from 1.0pg/mL to 1.0ng/mL and limit of detection down to 0.33pg/mL, which opened up a new research direction for ultrasensitive ECL bioanalysis based metal NCs.

Histone Deacetylase 3 Inhibitor Suppresses Hepatitis C Virus Replication by Regulating Apo-A1 and LEAP-1 Expression.

Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the effect of HDAC inhibitor treatment on hepatitis C virus (HCV) replication in Huh7 human liver cells and in a mouse model of HCV infection. Viral replication was markedly suppressed by the HDAC3 inhibitor at concentrations below 1 mmol/L, with no cellular toxicity. This was accompanied by upregulation of liver-expressed antimicrobial peptide 1(LEAP-1) and downregulation of apolipoprotein-A1 (Apo-A1), as determined by microarray and quantitative RT-PCR analyses. Moreover, HDAC3 was found to modulate the binding of CCAAT-enhancer-binding protein α (C/EBPα), hypoxia-inducible factor 1α (HIF1α), and signal transducer and activator of transcription 3 (STAT3) to the LEAP-1 promoter. HDAC3 inhibitor treatment also blocked HCV replication in a mouse model of HCV infection. These results indicate that epigenetic therapy with HDAC3 inhibitor may be a potential treatment for diseases associated with HCV infection such as HCC.