Discovery and Verification of Key Liver Cancer Genes and Alternative Splicing Events Based on Second-Generation Sequencing Data Analysis.

Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Existing screening and early diagnosis methods are not highly sensitive for HCC, and patients are likely to develop the disease to the middle and advanced stages before being diagnosed. Therefore, finding new and efficient diagnosis and treatment methods has become an urgent problem. We aimed at finding and verifying new liver cancer markers by combining informatics analysis with experimental exploration to provide new ideas and methods for the diagnosis and treatment of clinical liver cancer. We used two different bioinformatic pipelines to analyze sequencing data of clinical liver cancer samples and identify differentially expressed genes and key variants after combining them with The Cancer Genome Atlas sequencing data. Then, we explored the functions and mechanisms of the key variants to identify potential liver cancer markers. Through bioinformatic analysis of sequencing data, 139 differentially expressed genes were found, including 53 upregulated genes and 86 downregulated genes. Through enrichment and alternative splicing event analysis of sequencing data, we found nine key variants with exon skipping events. Metallothionein 1E (MT1E)-203 was found to be a key variant that influenced cell proliferation through the p53 cell cycle pathway through cell viability and proliferation assays, and MT1E-203 lost the ability to bind two zinc ions due to exon skipping according to the structure prediction of MT1E-203. MT1E-203 is a potential biomarker for HCC and may play an important role in the diagnosis and treatment of HCC.

Increased Non-switched Memory B Cells are Associated with Plasmablasts, Serum IL-6 Levels and Renal Functional Impairments in IgAN Patients.

Background: Circulating B cells are crucial for the pathogenesis of IgA nephropathy (IgAN). This study aimed at investigating the relationship between frequency of different subsets of circulating B cells and clinical measures in IgAN patients.Methods: The percentages of different subsets of circulating B cells in 23 IgAN patients and 14 healthy controls (HC) were determined by flow cytometry. Their serum IL-6 levels were measured by Cytometric Bead Array (CBA). Clinical parameters in five patients were measured before and after treatment for 8-12 weeks. The potential relationship between variants was analyzed.Results: In comparison with the HC, the frequency of CD3-CD19+ CD27+ IgD+IgM+ non-switched memory B cells (P = .0038) and CD3-CD19+ CD27hiCD38hi plasmablasts (P = .0467) and serum IL-6 (P = .0392) levels significantly increased in IgAN patients. The percentages of non-switched memory B cells were positively correlated with plasmablasts (R = 0.5781, P = .0039) and serum IL-6 levels (R = 0.6663, P = .0005) in the patients. The percentages of non-switched memory B cells (R = 0.8399, P < .0001), plasmablasts (R = 0.4486, P = .0318) and the levels of serum IL-6 (R = 0.5461, P = .0070) were positively correlated with the values of 24-h urine proteins in IgAN patients. The serum levels of IL-6 were negatively correlated with the eGFR values. Following standard treatment, the frequency of non-switched memory B cells and plasmablasts and the levels of 24-h urine proteins (P = .0317, P = .0079, P < .05) significantly decreased in IgAN patients.Conclusions: Abnormally higher frequency of non-switched memory B cells and plasmablasts may contribute to the pathogenesis of IgAN and be potential biomarkers for IgAN.

Oncogenic effect of PHLDB2 is associated with epithelial-mesenchymal transition and E-cadherin regulation in colorectal cancer.

BACKGROUND: Pleckstrin Homology Like Domain Family Member 2 (PHLDB2) is an important protein with a PH-domain for interaction with partners to regulate cell migration. However, the role of PHLDB2 in human cancer metastasis, especially in colon cancer, still remains elusive. METHODS: The RNA-seq and clinical data of colorectal cancer patients from the Cancer Genome Atlas (TCGA) were analyzed for correlations between PHLDB2 and clinical outcomes as well as epithelial-mesenchymal transition (EMT) markers. Wound healing and transwell invasion assays were used to determine the effects of PHLDB2 on cell migration and invasiveness. Western blot and qRT-PCR analyses were employed to detect protein and mRNA changes, respectively. Co-immunoprecipitation was performed to assess protein-protein interaction. RESULTS: In the present report, by following our previous study, we found that PHLDB2 expression is associated with poorer prognosis, including disease-free survival, tumor stage, nodes pathology, as well as lymphatic and vascular invasion through TCGA data analysis. In addition, PHLDB2 expression is highly correlated with multiple epithelial-mesenchymal transition (EMT) markers involving cell-surface proteins (N-cadherin and OB-cadherin), cytoskeletal markers (α-SMA and Vimentin), ECM proteins (Fibronectin and Laminin 5), and transcription factors (Snail2, ZEB1, and Ets-1). We also demonstrated that PHLDB2 knockdown mediated by siRNA was sufficient to attenuate colon cancer cell migration and invasion, as well as E-Cadherin reduction, by TGF-ß treatment. Interestingly, PHLDB2 expression levels were significantly elevated in response to EMT induction by TGF-ß and EGF. Moreover, we found that PHLDB2 could bind to MDM2 and facilitate MDM2-mediated E-Cadherin degradation. CONCLUSIONS: Our findings suggest that PHLDB2 is a downstream effector of EMT pathway and may present as an important biomarker for colon cancer prognosis and a target for colon cancer intervention.

Lipid metabolism participates in human membranous nephropathy identified by whole-genome gene expression profiling.

A genomics approach is an effective way to understand the possible mechanisms underlying the onset and progression of disease. However, very limited results have been published regarding whole-genome expression analysis of human idiopathic membranous nephropathy (iMN) using renal tissue. In the present study, gene expression profiling using renal cortex tissue from iMN patients and healthy controls was conducted; differentially expressed genes (DEGs) were filtered out, and 167 up- and 291 down-regulated genes were identified as overlapping DEGs (ODEGs). Moreover, enrichment analysis and protein-protein network construction were performed, revealing enrichment of genes mainly in cholesterol metabolism and arachidonic acid metabolism, among others, with 38 hub genes obtained. Furthermore, we found several associations between circulating lipid concentrations and hub gene signal intensities in the renal cortex. Our findings indicate that lipid metabolism, including cholesterol metabolism and arachidonic acid metabolism, may participate in iMN pathogenesis through key genes, including apolipoprotein A1 (APOA1), apolipoprotein B (APOB), apolipoprotein C3 (APOC3), cholesteryl ester transfer protein (CETP), and phospholipase A2 group XIIB (PLA2G12B).

Combinatory inhibition of TRIM65 and MDM2 in lung cancer cells.

In addition to the involvement in white matter lesion, tripartite-motif protein family member 65 (TRIM65) has also been implicated in tumorigenesis as a potential oncogene. However, the underlining mechanisms of TRIM65 functions and its clinical implication still remain to be further elucidated. In the present study, we found that TRIM65 binds to the N-terminus of p53 tumor suppressor and thus competes with MDM2 for p53 binding. Intriguingly, analysis of the Cancer Genome Atlas (TCGA) gene alteration database revealed that elevated expression of TRIM65 is mutually exclusive to MDM2 up-regulation in human lung adenocarcinoma patients, indicating potential compensatory effect of one over the other. Indeed, overexpression of TRIM65 renders lung cancer cell line resistance to Nutlin-3a, an effective MDM2 inhibitor, as determined by p53 activation and cell proliferation assays. Furthermore, depletion of TRIM65 using siRNA in combination with Nutlin-3a treatment demonstrates enhanced anti-tumor effects on lung cancer cell line. Collectively, our findings provide the rationale for developing strategies to target TRIM65 for lung cancer intervention, potentially in combination with MDM2 inhibition.

p53 target miR-29c-3p suppresses colon cancer cell invasion and migration through inhibition of PHLDB2.

miR-29c-3p is a potential tumor suppressor microRNA that is reportedly downregulated in several types of human cancers, but its role in colon cancer remains to be elucidated. Meanwhile, TP53, one of the most important tumor suppressors, is highly mutated in colon cancer. In the attempt to connect p53 and miR-29c-3p, we found that the upstream of miR-29c-3p gene contains a functional p53 consensus responsive element that is driven by p53 transcriptional factor activity, suggesting miR-29c-3p as a direct p53 target gene. Through online software prediction and in vivo validation, we demonstrated that Pleckstrin Homology Like Domain Family Member 2 (PHLDB2) is a valid miR-29c-3p target gene. Analysis of human cancer databases available from PROGgeneV2 showed that higher expression of PHLDB2 is associated with shorter overall survival and metastasis-free survival of colon cancer patients. Further, suppression of colon cancer cell invasion and migration by miR-29c-3p was significantly attenuated in the presence of ectopic PHLDB2, indicating PHLDB2 is a critical downstream target of miR-29c-3p. Collectively, our findings present the first to elucidate that miR-29c is a direct p53 target gene, and also identify PHLDB2 as an important miR-29c target gene involved in colon cancer metastasis.

TRIM65 negatively regulates p53 through ubiquitination.

Tripartite-motif protein family member 65 (TRIM65) is an important protein involved in white matter lesion. However, the role of TRIM65 in human cancer remains less understood. Through the Cancer Genome Atlas (TCGA) gene alteration database, we found that TRIM65 is upregulated in a significant portion of non-small cell lung carcinoma (NSCLC) patients. Our cell growth assay revealed that TRIM65 overexpression promotes cell proliferation, while knockdown of TRIM65 displays opposite effect. Mechanistically, TRIM65 binds to p53, one of the most critical tumor suppressors, and serves as an E3 ligase toward p53. Consequently, TRIM65 inactivates p53 through facilitating p53 poly-ubiquitination and proteasome-mediated degradation. Notably, chemotherapeutic reagent cisplatin induction of p53 is markedly attenuated in response to ectopic expression of TRIM65. Cell growth inhibition by TRIM65 knockdown is more significant in p53 positive H460 than p53 negative H1299 cells, and knockdown of p53 in H460 cells also shows compromised cell growth inhibition by TRIM65 knockdown, indicating that p53 is required, at least in part, for TRIM65 function. Our findings demonstrate TRIM65 as a potential oncogenic protein, highly likely through p53 inactivation, and provide insight into development of novel approaches targeting TRIM65 for NSCLC treatment, and also overcoming chemotherapy resistance.

A method to label biological molecules with dsDNA coated gold nanoparticles.

We described a new method to label biological molecules using gold nanoparticles (GNPs) and double stranded DNA. Researchers can conveniently label their own samples with GNPs using this method. The label is based on dsDNA with a 93.5% coverage of GNPs (dsDNA:GNP = 303:1). Antigens, streptavidin and biotin were labeled on GNPs and the success of the method was investigated with agarose gel electrophoresis, laser particle size analysis and ultraviolet spectrophotometry. These analyses confirmed that biological molecules were successfully bound to the GNPs. These molecules retained their biological activity and were able to detect targets on PVDF and NC membranes with excellent selectivity and low levels of background. Modified GNPs were also able to detect targets on nylon membranes, but with some degree of false positives. The maximum limit of detection was 25 ng proteins.

(E)-1-[4-(3-Bromo-prop-oxy)phen-yl]-2-p-tolyl-diazene.

In the title mol-ecule, C(16)H(17)BrN(2)O, the benzene rings, bridged by a diazene fragment, form a dihedral angle of 6.3 (2)°. The crystal packing exhibits relatively short Br⋯Br contacts of 3.6989 (14) Å.

Efficacy analysis of targeted nanodrug for non-small cell lung cancer therapy.

Biological macromolecules have been widely used as biomedical carriers in treating non-small cell lung cancer (NSCLC) due to their biocompatibility, targeting, biodegradability, and antitumor efficacy. Nanotechnology has been used in clinics to treat many diseases, including cancer. Nanoparticles (NPs) can accumulate drugs into tumors because of their enhanced permeability and retention (EPR) effects. However, the lack of active targeting ligands affects NPs drug delivery. Arginine-glycine-aspartic (RGD), as a targeting ligand, has distinct advantages in targeting and safety. In the present study, an RGD peptide-modified nanogel called RGD-polyethylene glycol-poly (L-phenylalanine-co-L-cystine) (RGD-PEG-P (LP-co-LC-P (LP-co-LC) was investigated to deliver vincristine (VCR) as NSCLC therapy. The VCR-loaded targeted nanoparticle (RGD-NP/VCR) demonstrated excellent antitumor efficacy compared to the free drug (VCR) and untargeted nanoparticle (NP/VCR) without any significant side effects. RGD-NP/VCR has better tumor inhibition and fewer side effects, indicating its potential benefit in NSCLC treatment.

Molecular Cloning and Characterization of a Novel Exo-ß-1,3-Galactanase from Penicillium oxalicum sp. 68.

Arabinogalactans have diverse biological properties and can be used as pharmaceutical agents. Most arabinogalactans are composed of ß-(1→3)-galactan, so it is particularly important to identify ß-1,3-galactanases that can selectively degrade them. In this study, a novel exo-ß-1,3-galactanase, named PoGal3, was screened from Penicillium oxalicum sp. 68, and hetero-expressed in P. pastoris GS115 as a soluble protein. PoGal3 belongs to glycoside hydrolase family 43 (GH43) and has a 1,356-bp gene length that encodes 451 amino acids residues. To study the enzymatic properties and substrate selectivity of PoGal3, ß-1,3-galactan (AG-P-I) from larch wood arabinogalactan (LWAG) was prepared and characterized by HPLC and NMR. Using AG-P-I as substrate, purified PoGal3 exhibited an optimal pH of 5.0 and temperature of 40°C. We also discovered that Zn2+ had the strongest promoting effect on enzyme activity, increasing it by 28.6%. Substrate specificity suggests that PoGal3 functions as an exo-ß-1,3-galactanase, with its greatest catalytic activity observed on AG-P-I. Hydrolytic products of AG-P-I are mainly composed of galactose and ß-1,6-galactobiose. In addition, PoGal3 can catalyze hydrolysis of LWAG to produce galacto-oligomers. PoGal3 is the first enzyme identified as an exo-ß-1,3-galactanase that can be used in building glycan blocks of crucial glycoconjugates to assess their biological functions.

Application of Nanoparticles in the Treatment of Lung Cancer With Emphasis on Receptors.

Lung cancer is one of the malignant tumors that has seen the most rapid growth in terms of morbidity and mortality in recent years, posing the biggest threat to people's health and lives. In recent years, the nano-drug loading system has made significant progress in the detection, diagnosis, and treatment of lung cancer. Nanomaterials are used to specifically target tumor tissue to minimize therapeutic adverse effects and increase bioavailability. It is achieved primarily through two mechanisms: passive targeting, which entails the use of enhanced penetration and retention (EPR) effect, and active targeting, which entails the loading recognition ligands for tumor marker molecules onto nanomaterials. However, it has been demonstrated that the EPR effect is effective in rodents but not in humans. Taking this into consideration, researchers paid significant attention to the active targeting nano-drug loading system. Additionally, it has been demonstrated to have a higher affinity and specificity for tumor cells. In this review, it describes the development of research into active targeted nano-drug delivery systems for lung cancer treatment from the receptors' or targets' perspective. We anticipate that this study will help biomedical researchers use nanoparticles (NPs) to treat lung cancer by providing more and novel drug delivery strategies or solid ligands.

Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy.

The stimuli-responsive polymer-based platform for controlled drug delivery has gained increasing attention in treating hepatocellular carcinoma (HCC) owing to the fascinating biocompatibility and biodegradability, improved antitumor efficacy, and negligible side effects recently. Herein, a disulfide bond-contained polypeptide nanogel, methoxy poly(ethylene glycol)-poly(l-phenylalanine-co-l-cystine) [mPEG-P(LP-co-LC)] nanogel, which could be responsive to the intracellular reduction microenvironments, was developed to deliver lenvatinib (LEN), an inhibitor of multiple receptor tyrosine kinases, for HCC therapy. The lenvatinib-loaded nanogel (NG/LEN) displayed concise drug delivery under the stimulus of glutathione in the cancer cells. Furthermore, the intracellular reduction-responsive nanomedicine NG/LEN showed excellent antitumor effect and almost no side effects toward both subcutaneous and orthotopic HCC tumor-allografted mice in comparison to free drug. The excellent tumor-inhibition efficacy with negligible side effects demonstrated the potential of NG/LEN for clinical molecular targeted therapy of gastrointestinal carcinoma in the future.

Single and multiple dose pharmacokinetics and safety of ZSP1273, an RNA polymerase PB2 protein inhibitor of the influenza A virus: a phase 1 double-blind study in healthy subjects.

BACKGROUND: Influenza is an acute respiratory illness. Treating with antiviral drugs can decrease the duration of illness and serious complications . ZSP1273 is a small-molecule anti-influenza drug targeting the RNA polymerase PB2 subunit of the influenza virus. The aim of this clinical trial was to evaluate the safety and pharmacokinetics (PKs) of ZSP1273 in healthy subjects. RESEARCH DESIGN AND METHODS: This was a double-blind, placebo-controlled phase 1 study consisting of three parts. 100 volunteers were enrolled and randomized to receive either single or multiple doses of ZSP1273 or placebo. RESULTS: A total of 31 (31.0%) subjects experienced at least one mild or moderate adverse event. The linear regression relationship between dose and plasma Cmax, AUC0-t, and AUC0-∞ showed an increasing trend and rapid absorption of ZSP1273. A high-fat diet had little effect on the PKs. The plasma concentration of ZSP1273 reached steady state on day 5 without drug accumulation. CONCLUSIONS: ZSP1273 was safe in healthy volunteers. Based on the preclinical resuilts, safety profile and PK characteristics of ZSP1273, the dose of ZSP1273 (≥200 mg) may be used for future clinical trials in influenza patients. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03679143).

Combined strategy of blending and surface modification as an effective route to prepare antifouling ultrafiltration membranes.

Ultrafiltration (UF) membranes blended with hydrophilic nanomaterials usually exhibit preferable overall performance including the membrane permeability and antifouling capability. However, the improvement in antifouling performance may be not outstanding due to the small amount of nanomaterial distributed near the membrane surface and the limited improvement in membrane hydrophilicity. Notably, excess addition of nanomaterials may lead to the decline in membrane permeability. In order to solve the above problem, we integrated the strategy of blending and surface modification to construct novel hybrid UF membranes. Novel nanohybrid was prepared via tannic acid (TA) coating on hydroxyapatite nanotubes (HANTs) and the subsequent grafting of zwitterionic polyethylenimine (ZPEI). The prepared nanohybrid (HANTs@TA-ZPEI) was incorporated with the polysulfone containing tertiary amine groups to fabricate hybrid membranes via the solution blending and the subsequent immersion-precipitation phase inversion process. Then the matrix was modified with zwitterions via the reaction of tertiary amine group with 1, 3-propane sultone. UF tests were conducted using the bovine serum albumin (BSA) and humic acid (HA) as the representative foulants. Results showed that both the permeability and the antifouling performance of the membranes achieved favorable promotion. Thereinto, the water flux of M-B0.4-Z membrane (pre blended with 0.4 wt% HANTs@TA-ZPEI in the casting solution and post-surface modified) exhibited 2.6 times that of the pristine membrane and the flux recovery ratio (FRR) for BSA and HA attained 93.4% and 96.1%, respectively. By the combination of blending and surface modification, both the membrane permeability and fouling resistant properties could attain remarkable promotion, which exerted the advantages of two methods and made up the deficiency of single blending method.

Decreased number of CD19+CD24hiCD38hi regulatory B cells in Diabetic nephropathy.

BACKGROUND: Regulatory B cells participate in the pathogenesis of autoimmune disease. This study aimed to examine the putative contribution of regulatory B cells to the pathogenesis of DN. The number of circulating CD19+CD24hiCD38hi B cells, CD19+CD24hiCD38hiCD5+ B cells, and CD19+CD24hiCD38hiIL-10+ B cells were significantly lower in DN patients (p < 0.05) than the control group. The number of circulating CD19+CD24hiCD38hi B cells was positively correlated with the levels of eGFR and serum IL-10 levels, but negatively correlated with urinary protein levels in DN patients. Treatment significantly increased the number of CD19+CD24hiCD38hi B cells, CD19+CD24hiCD38hiCD5+ B cells, CD19+CD24hiCD38hiIL-10+ B cells, and the levels of serum IL-10 (p < 0.05). We conclude that regulatory B cells may present new targets for intervention of DN.

Role of Astrocytes in Post-traumatic Epilepsy.

Traumatic brain injury, a common cause of acquired epilepsy, is typical to find necrotic cell death within the injury core. The dynamic changes in astrocytes surrounding the injury core contribute to epileptic seizures associated with intense neuronal firing. However, little is known about the molecular mechanisms that activate astrocytes during traumatic brain injury or the effect of functional changes of astrocytes on seizures. In this comprehensive review, we present our cumulated understanding of the complex neurological affection in astrocytes after traumatic brain injury. We approached the problem through describing the changes of cell morphology, neurotransmitters, biochemistry, and cytokines in astrocytes during post-traumatic epilepsy. In addition, we also discussed the relationship between dynamic changes in astrocytes and seizures and the current pharmacologic agents used for treatment. Hopefully, this review will provide a more detailed knowledge from which better therapeutic strategies can be developed to treat post-traumatic epilepsy.

Role of Adaptive and Innate Immunity in Type 2 Diabetes Mellitus.

After the recognition of the essential role of the immune system in the progression of type 2 diabetes mellitus, more studies are focused on the effects produced by the abnormal differentiation of components of the immune system. In patients suffering from obesity or T2DM, there were alterations in proliferation of T cells and macrophages, and impairment in function of NK cells and B cells, which represented abnormal innate and adaptive immunity. The abnormality of either innate immunity, adaptive immunity, or both was involved and interacted with each other during the progression of T2DM. Although previous studies have revealed the functional involvement of T cells in T2DM, and the regulation of metabolism by the innate or adaptive immune system during the pathogenesis of T2DM, there has been a lack of literature reviewing the relevant role of adaptive and innate immunity in the progression of T2DM. Here, we will review their relevant roles, aiming to provide new thought for the development of immunotherapy in T2DM.

Influence of Air Pollution on Hospital Admissions in Adult Asthma in Northeast China.

BACKGROUND: Asthma is a common chronic respiratory disease and is related to air pollution exposure. However, only a few studies have concentrated on the association between air pollution and adult asthma. Moreover, the results of these studies are controversial. Therefore, the present study aimed to analyze the influence of various pollutants on hospitalization due to asthma in adults. METHODS: A total of 1019 unrelated hospitalized adult asthma patients from Northeast China were recruited from 2014 to 2016. Daily average concentrations of air pollutants (particulate matter <2.5 µm [PM2.5], particulate matter <10 µm [PM10], sulfur dioxide [SO2], nitrogen dioxide [NO2], and carbon monoxide [CO]) were obtained from the China National Environmental Monitoring Centre website from 2014 to 2016. Cox logistic regression analysis was used to analyze the relationship between air pollutants and hospital admissions in adult asthma. RESULTS: The maximum odds ratio (OR) value for most air pollutants occurred on lag day 1. Lag day 1 was chosen as the exposure period, and 8 days before onset was chosen as the control period. Three pollutants (PM2.5, CO, and SO2) were entered into the regression equation, and the corresponding OR (95% confidence interval) was 0.995 (0.991-0.999), 3.107 (1.607-6.010), and 0.979 (0.968-0.990), respectively. CONCLUSIONS: A positive association between hospital admissions and the daily average concentration of CO was observed. CO is likely to be a risk factor for hospital admissions in adults with asthma.

Hypolipidemic effects of total flavonoide extracted from the leaves of Actinidiakolomikta in rats fed a high-fat diet.

OBJECTIVES: This study was to investigate the antihyperlipidemic and antioxidant effect of total flavonoid extract from Actinidiakolomikta (TFAK) in hyperlipidemia induced by a high-fat diet. MATERIALS AND METHODS: Male SD rats were randomly divided into 6 groups: normal group, model (hyperlipidemic diet) group, hyperlipedemic diet supplemented with TFAK (50, 100 and 200 mg/kg) and simvastatin (30 mg/kg) groups. The rats were administrated TFAK by oral for 28 days. Body weight, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), superoxide dismutase (SOD), catalase(CAT), glutathione peroxidase(GSH-Px) and malondialdehyde (MDA) were measured. The atherogenic index (AI) and coronary risk index (CRI) were calculated. The activity of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase in hepatic tissue was examined. Histopathologic changes were also checked. RESULTS: The levels of TC, TG and LDL-c were increased in model group. Compared to the model group, TFAK reduced significantly the body weight, TC, TG, LDL-c, AI, CRI and elevated the level of HDL-c. Moreover, the activity of SOD was elevated significantly, whereas the content of MDA decreased. The activity of HMG-CoA reductase was also decreased. Morphological evaluation found that rats in model group developed a severe steatosis, but the severity of liver steatosis was ameliorated in TFAK treated groups. The possible mechanism may be associated with decrease HMG-CoA reductase activity. CONCLUSION: Our results suggest that TFAK exerts strong antioxidant and lipid-lowering effects, prevents hepatic fatty deposition and regulates the HMG-CoA reductase.