Regulation of heterogeneous electron transfer reactivity by defect engineering through electrochemically induced brominating addition.

Enhancing the electrochemical activity of graphene holds great significance for expanding its applications in various electrochemistry fields. In this study, we have demonstrated a facile and quantitative approach for modulating the defect density of single-layer graphene (SLG) via an electrochemically induced bromination process facilitated by cyclic voltammetry. This controlled defect engineering directly impacts the heterogeneous electron transfer (HET) rate of SLG. By utilizing Raman spectroscopy and scanning electrochemical microscopy (SECM), we have established a correlation between the HET kinetics and both the defect density (nD) and mean distance between defects (LD) of SLG. The variation of the HET rate (k0) with the defect density manifested a distinctive three-stage behavior. Initially, k0 increased slightly with the increasing nD, and then it experienced a rapid increase as nD further increased. However, once the defect density surpassed a critical value of about 1.8 × 1012 cm-2 (LD < 4.2 nm), k0 decreased rapidly. Notably, the results revealed a remarkable 35-fold enhancement of k0 under the optimal defect density conditions compared to pristine SLG. This research paves the way for controllable defect engineering as a powerful strategy to enhance the electrochemical activity of graphene, opening up new possibilities for its utilization in a wide range of electrochemical applications.

Ultrasonic-Assisted Electrochemical Nanoimprint Lithography: Forcing Mass Transfer to Enhance the Localized Etching Rate of GaAs.

Electrochemical nanoimprint lithography (ECNL) has emerged as a promising technique for fabricating three-dimensional micro/nano-structures (3D-MNSs) directly on semiconductor wafers. This technique is based on a localized corrosion reaction induced by the contact potential across the metal/semiconductor boundaries. The anodic etching of semiconductor and the cathodic reduction of electron acceptors occur at the metal/semiconductor/electrolyte interface and the Pt mold surface, respectively. However, the etching rate is limited by the mass transfer of species in the ultrathin electrolyte layer between the mold and the workpiece. To overcome this challenge, we introduce the ultrasonics effect into the ECNL process to facilitate the mass exchange between the ultrathin electrolyte layer and the bulk solution, thereby improving the imprinting efficiency. Experimental investigations demonstrate a positive linear relationship between the reciprocal of the area duty ratio of the mold and the imprinting efficiency. Furthermore, the introduction of ultrasonics improves the imprinting efficiency by approximately 80 %, irrespective of the area duty ratio. The enhanced imprinting efficiency enables the fabrication of 3D-MNSs with higher aspect ratios, resulting in a stronger light trapping effect. These results indicate the prospective applications of ECNL in semiconductor functional devices, such as photoelectric detection and photovoltaics.

Modulation of pre-neoplastic biomarkers induced by sequential aflatoxin B1 and fumonisin B1 exposure in F344 rats treated with UPSN clay.

Populations consuming aflatoxin (AF) and fumonisin (FN)-contaminated foods may be at increased risk for hepatocellular carcinoma (HCC) and developmental disorders; consequently, development of intervention strategies to reduce AF/FN-induced liver disease and adverse health effects in humans could be very useful. Calcium montmorillonite clay (NovaSil) has been shown to absorb AF in vitro, in multiple animal models, as well as in human studies. In the present study, we aimed to evaluate whether uniform particle size NovaSil (UPSN) possessed an ability to modulate the co-carcinogenic potentials of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) in F344 rats. Sequential treatment of FB1 following AFB1 synergistically induces preneoplastic alterations as well as liver damage, indicating that AFB1 acts as an initiator while FB1 as a promoter in the carcinogenesis model, confirming findings from previous studies. The enterosorbent agent UPSN clay at dose of up to 0.5% in diet was shown to be effective in modulating the toxicity and carcinogenicity of co-exposure to AFB1 and FB1, as demonstrated by significant reduction in number and size of hepatic GST-P+ foci, in alterations indicative of liver toxicity, and in levels of AFB1 and FB1 biomarkers.

Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.

Dietary co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) and their interaction on hepatocellular carcinogenesis is of particular concern in toxicology and public health. In this study we evaluated the liver preneoplastic effects of single and sequential dietary exposure to AFB1 and FB1 in the F344 rat carcinogenesis model. Serum biochemical alterations, liver histopathological changes, and the formation of liver glutathione S transferase positive (GST-P+) foci were the major outcome parameters examined. Compared to the AFB1-only treatment, the FB1-only treatment induced less dysplasia, and more apoptosis and mitoses. Sequential AFB1 and FB1 treatment lead to increased numbers of dysplasia, apoptosis and foci of altered hepatocytes, as compared to either mycotoxin treatment alone. More importantly, sequential exposure to AFB1 and FB1 synergistically increased the numbers of liver GTP-P+ foci by approximately 7.3-and 12.9-fold and increased the mean sizes of GST-P+ foci by 6- and 7.5-fold, respectively, as compared to AFB1- or FB1-only treatment groups. In addition, liver ALT and AST levels were significantly increased after sequential treatment as compared to single treatment groups. The results demonstrate the interactive effect of dietary AFB1 and FB1 in inducing liver GST-P+ foci formation and provide information to model future intervention studies.

Identification of key genes in hepatocellular carcinoma and validation of the candidate gene, cdc25a, using gene set enrichment analysis, meta-analysis and cross-species comparison.

The aim of the present study was to determine key pathways and genes involved in the pathogenesis of hepatocellular carcinoma (HCC) through bioinformatic analyses of HCC microarray data based on cross-species comparison. Microarray data of gene expression in HCC in different species were analyzed using gene set enrichment analysis (GSEA) and meta-analysis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to determine the mRNA and protein expression levels of cdc25a, one of the identified candidate genes, in human, rat and tree shrew samples. The cell cycle pathway had the largest overlap between the GSEA and meta-analysis. Meta-analyses showed that 25 genes, including cdc25a, in the cell cycle pathway were differentially expressed. Cdc25a mRNA levels in HCC tissues were higher than those in normal liver tissues in humans, rats and tree shrews, and the expression level of cdc25a in HCC tissues was higher than in corresponding paraneoplastic tissues in humans and rats. In human HCC tissues, the cdc25a mRNA level was significantly correlated with clinical stage, portal vein tumor thrombosis and extrahepatic metastasis. Western blotting showed that, cdc25a protein levels were significantly upregulated in HCC tissues in humans, rats and tree shrews. In conclusion, GSEA and meta-analysis can be combined to identify key molecules and pathways involved in HCC. This study demonstrated that the cell cycle pathway and the cdc25a gene may be crucial in the pathogenesis and progression of HCC.

Mitigation of Fumonisin Biomarkers by Green Tea Polyphenols in a High-Risk Population of Hepatocellular Carcinoma.

Green tea polyphenols (GTP) are highly effective in inhibiting a variety of tumorigenic effects induced by carcinogens. In this study we assessed GTP mitigation on biomarkers of fumonisin B1 (FB1), a class 2B carcinogen, in blood and urine samples collected from an intervention trial. A total of 124 exposed people were recruited and randomly assigned to low-dose (GTP 500 mg, n = 42), high-dose (GTP 1,000 mg, n = 41) or placebo (n = 41) for 3 months. After one-month of intervention, urinary FB1 was significantly decreased in high-dose group compared to that of placebo group (p = 0.045), with reduction rates of 18.95% in the low-dose group and 33.62% in the high-dose group. After three-month intervention, urinary FB1 showed significant decrease in both low-dose (p = 0.016) and the high-dose (p = 0.0005) groups compared to that of both placebo group and baseline levels, with reduction rates of 40.18% in the low-dose group and 52.6% in the high-dose group. GTP treatment also significantly reduced urinary excretion of sphinganine (Sa), sphingosine (So), and Sa/So ratio, but had no effect on serum Sa, So, and Sa/So ratio. Analysis with mixed-effect model revealed significant interactions between time and treatment effects of GTP on both urinary free FB1 levels and Sa/So ratios.

Broadband high-power mid-IR femtosecond pulse generation from an ytterbium-doped fiber laser pumped optical parametric amplifier.

We report on a high-power periodically poled MgO-doped lithium niobate (MgO:PPLN)-based femtosecond optical parametric amplifier (OPA), featuring a spectral seamless broadband mid-infrared (MIR) output. By modifying the initial chirp and spectrum of the mode-locked seed laser, the Yb fiber pump laser exhibits a final output power of 14 W with sub-200-fs pulse duration after power amplification and compression. When the OPA was seeded with a broadband amplified spontaneous emission (ASE) source, a damage-limited 0.6 W broadband MIR radiation was experimentally obtained under the pump power of 10.15 W at 82 MHz repetition rate, corresponding to an overall OPA conversion efficiency of 32.7%. The 3 dB bandwidth of the mid-IR idler was 291.9 nm, centering at 3.34 µm.

Chronic hepatitis B virus infection and occurrence of hepatocellular carcinoma in tree shrews (Tupaia belangeri chinensis).

BACKGROUND: Hepatitis B virus (HBV) infection has been believed as a major cause of hepatocellular carcinoma (HCC) for a long time, however, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments. Tree shrew (Tupaia) is a small animal closely related to primates evolutionarily, with about 8 years of lifespan. Our previous study proved that tree shrews can be chronically HBV-infected after being inoculated neonatally with HBV. The present study reports the further results from the longer-term observation of these animals. METHODS: Neonatal tree shrews were inoculated with sera from HBV-infected patient or tree shrew. Their serum samples and liver biopsies were collected periodically for detection of HBV markers as well as for histopathological and immunohistochemical examinations. Group A consisted of six tree shrews with chronic HBV-infection, and group B consisted of nine tree shrews without chronic HBV infection. RESULTS: Periodical examinations on serum and liver biopsies of the animals in group A showed the progress of HBV infection, and two cases of HCC occurred at their late stage of life. The courses of HBV infection and the hepatic histopathological and immunohistochemical changes in the tree shrews were similar to those in humans. In contrast, neither HCC nor obvious hepatitis histopathological change was found among the tree shrews in group B. CONCLUSIONS: The course of HBV infection and the features of HCC discovered in tree shrews are similar to those of chronically HBV-infected humans. The tree shrew model might be used to investigate the underlying mechanisms favoring susceptibility for chronic HBV infection and disease progression.

[Expressions and significance of TLR2 and TLR4 in Kupffer cells of tree shrews chronically infected with hepatitis B virus].

OBJECTIVE: To investigate the mRNA expression levels of Toll-like receptors 2 (TLR2) and TLR4 in Kupffer cells of tree shrews that were chronically infected with hepatitis B virus (HBV), and the effects of these receptors on the function of Kupffer cells. METHODS: The tree shrews were divided into tree shrews proved with chronic HBV infection, tree shrews suspected with chronic HBV infection, and normal control tree shrews without hepatitis B vaccination. The samples of serum and liver biopsy were collected periodically, and the levels of HBV DNA in serum and liver tissues were detected by fluorescence-based quantitative real-time PCR (qRT-PCR). Meanwhile, Kupffer cells were isolated from the biopsied liver tissues, and then purified and primarily cultured. Afterwards, qRT-PCR was applied to detect the mRNA expression levels of TLR2, TLR4 and TNF-α in the Kupffer cells. Cell migration assay and lysosome-specific fluorescent probe were adopted to analyze the effects of TLR2 and TLR4 on the migration capacity of Kupffer cells and the quantity of lysosomes in these cells. RESULTS: The mRNA expression levels of TLR2 and TLR4 in tree shrews proved with chronic HBV infection were lower than those in the ones suspected with chronic HBV infection and normal controls without hepatitis B vaccination (P<0.05), and these expression levels were all negatively correlated with the level of HBV DNA in liver tissues of the animals (P<0.05), but were positively correlated with the number of migrated Kupffer cells, the density of lysosomes and the mRNA expression level of TNF-α (P<0.05). CONCLUSION: TLR2 and TLR4 in Kupffer cells may play important roles in the chronic process of hepatic pathological changes in tree shrews infected with HBV through their influence on the function of Kupffer cells.

Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats.

Aflatoxin B1 (AFB1) is immunotoxic to animals and a suspected immunosuppressant in humans. In this study, we investigated the effects of AFB1 on splenic lymphocyte phenotypes and the inflammatory cytokine expression in male F344 rats. Exposure of animals to AFB1 [5-75 µg kg(-1) body weight (BW)] for 1 week showed dose-dependent decreases in the percentage of splenic CD8(+) T cells and CD3(-) CD8a(+) NK cells. A general inhibition of the expression of interleukin (IL)-4 and interferon (IFN)-γ by CD4(+) T cells, IL-4 and IFN-γ by CD8a(+) cells, and tumor necrosis factor (TNF)-α expression by natural killer (NK) cells was also found; however, no concurrent histological changes in spleen tissue were present, suggesting acute immunosuppression without overt toxicity. Five-week exposure with AFB1 significantly increased the percentages of CD3(+) and CD8(+) T cells, especially at low doses (≤ 25 µg kg(-1)). AFB1 treatment significantly decreased the anti-inflammatory cytokine IL-4 expression by CD4(+) T cells and significantly increased the pro-inflammatory cytokine IFN-γ expression by CD4(+) T cells and TNF-α expression by NK cells. These results indicated that repeated AFB1 exposure promotes inflammatory responses by regulating cytokine expression. Our data provides novel insights into the mechanisms by which AFB1 exposure differentially modulates the cell-mediated immune responses and suggests the involvement of an inflammatory response upon repeated exposure.

Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST-Pi in rats with hepatocellular carcinoma risk.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers worldwide, and the pathogenesis is complicated at present. There iare few effective therapeutic measures, and novel therapeutic strategies are urgently required to improve clinical outcome. Ginkgo biloba extract (EGb) is reported to have an anti-cancer activity. OBJECTIVES: To explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi (GST-Pi) in the pathogenesis of HCC. METHODS: 120 Wistar rats were divided into three groups at random: normal control group (control group), HCC risk group without treatment (HCC risk group), HCC risk group treated with EGb (EGb group); n=40, respectively. The HCC risk in rat was induced by aflatoxin B1 injection. At the end of 13-week, 33-week, 53-week and 73-week, 10 rats in each group were killed and the relevant samples were collected. RESULTS: The mRNA and protein expressions of Cox-2 and GST-Pi were measured by real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and western-blot. When compared with those in the control group in 73-week, the mRNA and protein expressions of GST-Pi in EGb group were weaker than those in HCC risk group in 73-week. However, the mRNA and protein expressions of Cox-2 in HCC risk group were increased than that of control group, and there was no statistical difference for mRNA and protein expressions of Cox-2 between HCC risk group and EGb group. CONCLUSION: EGb can regulate the expression of GST-Pi, but it does not seem to have an effect on Cox-2 expression in the liver of HCC risk rats.

Histopathological changes in the liver of tree shrew (Tupaia belangeri chinensis) persistently infected with hepatitis B virus.

BACKGROUND: An animal model for HBV that more closely approximates the disease in humans is needed. The tree shrew (Tupaia belangeri) is closely related to primates and susceptible to HBV. We previously established that neonatal tree shrews can be persistently infected with HBV in vivo, and here present a six year follow-up histopathological study of these animals. METHODS: Group A consists of six tree shrews with persistent HBV infection, group B consists of three tree shrews with suspected persistent HBV infection, while group C consists of four tree shrews free of HBV infection. Serum and liver tissues samples were collected periodically from all animals. HBV antigen and HBV antibodies were detected by ELISA and/or TRFIA. HBV DNA in serum and in liver biopsies was measured by FQ-PCR. Liver biopsies were applied for general histopathologic observation and scoring, immunohistochemical detections of HBsAg and HBcAg, and ultrastructural observation with electron microscope technique. RESULTS: Hydropic, fatty and eosinophilic degeneration of hepatocytes, lymphocytic infiltration and hyperplasia of small bile ducts in the portal area were observed in group A. One animal infected with HBV for over six years showed multiple necrotic areas which had fused to form bridging necrosis and fibrosis, and megalocytosis. The hepatic histopathological scores of group A were higher than those of group B and C. The histopathological score correlated positively with the duration of infection. CONCLUSIONS: Hepatic histopathological changes observed in chronically HBV-infected tree shrews are similar to those observed in HBV-infected humans. The tree shrew may represent a novel animal model for HBV infection.

Integrative toxicopathological evaluation of aflatoxin B1 exposure in F344 rats.

In this study, male F344 rats were orally exposed to a single dose of aflatoxin B1 (AFB1) at 0, 50, 250, or 1,000 µg/kg body weight (BW) or repeated dose of 0, 5, 10, 25, or 75 µg/kg BW for up to 5 weeks. Biochemical and histological changes were assessed together with the formation of AFB1-lysine adduct (AFB-Lys) and liver foci positive for placental form glutathione S transferase (GST-P⁺). In single-dose protocol, serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed dose-related elevation, with maximal changes observed (>100-fold) at day 3 after treatment. Animals that received 250 µg/kg AFB1 showed concurrent bile duct proliferation, necrosis, and GST-P⁺ hepatocytes at 3 day, followed by liver GST-P⁺ foci appearance at 1 week. In repeated-dose protocol, bile duct proliferation and liver GST-P⁺ foci co-occurred after 3-week exposure to 75 µg/kg AFB1, followed by proliferation foci formation after 4 week and dramatic ALT, AST, and CK elevations after 5 weeks. Liver GST-P⁺ foci were induced temporally and in a dose-related manner. Serum AFB-Lys increased temporally at low doses (5-25 µg/kg), and reached the maximum after 2-week exposure at 75 µg/kg. This integrative study demonstrated that liver GST-P⁺ cells and foci are sensitive biomarkers for AFB1 toxic effect and correlated with bile duct proliferation and biochemical alterations in F344 rats.

[Factors influencing long-term hepatitis B virus infection of the tree shrew (Tupaia belangeri chinensis) as an in vivo model of chronic hepatitis B].

OBJECTIVE: To determine the methods for establishing an in vivo model of long-term hepatitis B virus (HBV) infection in the Chinese tree shrew (Tupaia belangeri chinensis). METHODS: Seventy-seven neonate (1-3 days old) and 49 young adult (2 weeks to 1 year old) tree shrews were inoculated with different HBV sources (chronic hepatitis B (CHB) human patient serum, single or pooled; HBV-infected tree shrew serum, single only; HBV-infected HepG2.2.15 cells' culture medium supernatant; HBV genome-transfected HepG2.2.15 cells' culture medium supernatant) through various routes of injection (subcutaneous, intraperitoneal, and direct liver via abdominal skin; adults also received intravenous and indirect liver via spleen). Serum and liver biopsies were collected from the animals at various time points post-inoculation for detection of HBV markers by fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, time-resolved immunofluorescence, Southern blotting, dot blotting, immunohistochemistry, and microscopy. RESULTS: Among the neonatal group of tree shrews, six (7.8%) were confirmed as HBV-infected for more than 72 (up to 228) weeks after inoculation and another seven (9.1%) were suspected of persistent infections. None of the young adult tree shrews developed persistent infection. Inoculation with single-source serum from either CHB humans or tree shrews were responsible for the most cases of infections, and the subcutaneous injection produced more infections than the other inoculation routes. The most reliable methods of determining HBV infection status were detection of serum HBV immunoreactive markers and intrahepatic HBV DNA. CONCLUSION: In order to establish an in vivo model of CHB in the tree shrew, the animals should be inoculated in the neonatal period using subcutaneous injection.

[Expression of epidermal fatty acid-binding protein in cross-species hepatocellular carcinoma].

OBJECTIVE: To evaluate the utility of the cross-species screening strategy for investigating key molecule(s) involved in onset and progression of hepatocellular carcinoma (HCC). METHODS: HCC-related molecule data from our previous studies and in the literature were collected to establish a cross-species dataset. Tissue samples of HCC, non-HCC surrounding liver (para-HCC), and normal liver that were collected from humans, tree shrews and rats. The genes reported to have the most differential expression in HCC were verified by analyzing the mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: The cross-species dataset of HCC-related molecules included four genes: epidermal fatty acid-binding protein (E-FABP), liver (L)-FABP, tyrosine a-ketoglutarate transaminase (TKT), and cytokeratin (CK8). In humans, E-FABP mRNA expression was significantly higher (P less than 0.05) in HCC (0.87+/-0.14 vs. para-HCC: 0.64+/-0.12 and normal liver: 0.67+/-0.07; F=20.910). Similar results were obtained in tree shrew (HCC: 0.87 +/- 0.25 vs. para-HCC: 0.73 +/- 0.19 and normal liver: 0.68+/-0.19; F=3.807) and rat (HCC: 0.97+/-0.22 vs. para-HCC: 0.78+/-0.16 and normal liver: 0.80 +/- 0.13; F=4.482). The Western blotting analyses revealed a similar statistically significant trend. CONCLUSION: The cross-species screening strategy for tumor genes may represent a feasible and convenient process of identifying key molecule(s) for human HCC. E-FABP may be a particularly crucial molecule for hepatocarcinogenesis.

Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): a model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans.

BACKGROUND: Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. RESULTS: Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. CONCLUSIONS: Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.

Electrochemically-driven large amplitude pH cycling for acid-base driven DNA denaturation and renaturation.

In this paper, we present an electrochemically driven large amplitude pH alteration method based on a serial electrolytic cell involving a hydrogen permeable bifacial working electrode such as Pd thin foil. The method allows solution pH to be changed periodically up to ±4~5 units without additional alteration of concentration and/or composition of the system. Application to the acid-base driven cyclic denaturation and renaturation of 290 bp DNA fragments is successfully demonstrated with in situ real-time UV spectroscopic characterization. Electrophoretic analysis confirms that the denaturation and renaturation processes are reversible without degradation of the DNA. The serial electrolytic cell based electrochemical pH alteration method presented in this work would promote investigations of a wide variety of potential-dependent processes and techniques.

[Progress on establishment of tree shrew (Tupaia) chronic infection with HBV in vivo].

Hepatitis B virus (HBV) infection is one of the important health problems worldwide, especially in China. Feasible and effective animal models of HBV infection in vivo are prerequisite for the HBV-related basic and clinical studies. Located in the highly prevalent region of HBV and hepatocellular carcinoma (HCC), the laboratory of Guangxi Cancer Institute has focused on the cause, pathogenesis and chemoprevention of HCC, and has started the work of establishing tree shrew (Tupaia) models of HBV infection in vivo since the early 1980s. This paper provides an overview of the research process, and highlights the new progress on the chronic infection of tree shrews after inoculated with HBV neonatally in vivo.

[Effects of AKR1B10 gene silence on the growth and gene expression of HCC cell line MHCC97H].

OBJECTIVE: To explore the biological function and possible underlying mechanism of aldo-keto reductase family 1 member B10 (AKR1B10) gene during hepatocarcinogenesis. METHODS: A pair of chemically synthesized small interfering RNA (siRNA) targeting on AKR1B10 was transfected into liver cancer cell line MHCC97H by LipofectamineTM 2000. After confirming the interfering effects of AKR1B10-siRNAs through Quant SYBR Green polymerase chain reaction (Real-time PCR), Western blot and enzymatic activity assay, the capabilities of proliferation and apoptosis of the transfected cells were observed by CCK-8 assay and flow cytometry analysis, and the expressions of a group of tumor-related gene such as c-myc, c-fos, N-ras were observed through Real-time PCR. RESULTS: The expressions of AKR1B10 and the enzymatic activity were down-regulated significantly in AKR1B10-siRNA-transfected cells. Compared with mock and blank control groups, cell growth in AKR1B10-siRNA-transfected group was inhibited by 26.6%+/-3.1% at 72h after transfection. The ratio of apoptotic cells was 37.3%+/-1.0% in AKR1B10-siRNA-transfected group, which was significantly higher than that in mock and blank control groups (P < 0.01). Real-time PCR showed that the expressions of oncogene c-myc, c-fos and N-ras, and the proliferation-associated gene ki-67 were down-regulated in AKR1B10-siRNA-transfected cells, while the expressions of apoptosis-promoting gene caspas-3 and bax were up-regulated. CONCLUSIONS: AKR1B10 might promote proliferation, inhibit apoptosis and then induce malignant transformation of hepatocytes by regulating the expression level of some tumor-related genes.

Genetic variations of hepatitis B virus and serum aflatoxin-lysine adduct on high risk of hepatocellular carcinoma in Southern Guangxi, China.

BACKGROUND & AIMS: Southern Guangxi area is one of the endemic areas for hepatocellular carcinoma (HCC) in China. This study evaluates the roles of genetic variations of hepatitis B virus (HBV) and aflatoxin B(1) (AFB(1)) exposure in the formation of HCC in this high-risk area. METHODS: The study recruited 60 HCC patients and 120 age-, gender-, and residency-matched controls. HBV genotype and basic core promoter (BCP) mutations were determined by nested-PCR/direct sequencing. Serum AFB(1)-lysine adduct was measured by high performance liquid chromatography-fluorescence detection. RESULTS: HBV genotype C was predominant in 75.0% of cases and 84.2% of controls. The 1762(T)/1764(A) double mutations, 1753(V) mutations, and 1752(V) mutations were associated with HCC risk evidenced by the adjusted odds ratio (OR) [95% confidence interval (95% CI)] of 3.89 (1.40-10.77), 2.87 (1.49-5.49), and 5.96 (1.75-20.25), respectively. The adjusted OR (95% CI) was 6.94 (1.68-27.78) for subjects with 1762(T)/1764(A) double mutations and high AFB(1)-lysine adduct level; 2.01 (0.24-14.29), for those with only 1762(T)/1764(A) double mutations; and 4.26 (1.16-15.38) for those with only high AFB(1)-lysine adduct level, respectively. The adjusted OR was 5.13 (1.79-14.71) for subjects with 1753(V) mutations and high AFB(1)-lysine adduct level; 1.20 (0.47-3.08) for those with only 1753(V) mutations, and 2.28 (1.01-5.31) for those with high AFB(1)-lysine adduct level, respectively. CONCLUSIONS: These data confirmed the association of BCP mutations with HCC risk and the additive effects of 1762(T)/1764(A) double mutations and 1753(V) mutations with dietary AFB(1) exposure in this high-risk area for HCC.