Gaucher-Associated Parkinsonism.

Gaucher disease is associated with Parkinson's disease (PD) by mutations in glucocerebrosidase (GCase). The gene encoding GCase, glucosidase beta acid (GBA), is an important risk factor for PD. Findings from large studies have shown that patients with PD have an increased frequency of mutations in GBA and that GBA mutation carriers exhibit diverse parkinsonian phenotypes and Lewy body pathology. Although the mechanism for this association remains elusive, some hypotheses have been proposed to explain it, including gain of function caused by GBA mutations, which increases α-synuclein (α-syn) aggregation, loss of function due to lysosomal enzyme deficiency, which affects α-syn clearance, and even a bidirectional feedback loop, but each of these hypotheses has its limitations. It is also worth noting that many findings have implicated the interaction between α-syn and GCase, indicating the essential role of the interaction in the pathogenesis of GBA-associated parkinsonism. Therefore, the current review focuses on α-syn and GCase, and it provides some new thoughts that may be helpful for understanding the α-syn-GCase interaction and unraveling the exact mechanism underlying GBA-associated parkinsonism.

Corporate digital transformation, internal control and total factor productivity.

Based on Resource-based theory and Internal Control (IC) theory, this study elucidates the impacts of corporate digital transformation on total factor productivity, and IC effectiveness, as well as the mechanism among digital transformation, IC and total factor productivity. The results show that digital transformation promotes total factor productivity and IC effectiveness. And effective IC has a significant mediating effect for the impact of digital transformation on total factor productivity. Heterogeneity discussion shows that compared with high-tech enterprises, in non-high-tech ones, digital transformation increases total factor productivity, and more significantly enhances IC effectiveness, presenting a mechanism that digital transformation facilitates IC, and increases total factor productivity. For non-high-tech enterprises, with higher heterogeneity of executive education backgrounds, digital transformation promotes IC effectiveness and total factor productivity, showing the transmission effect among digital transformation, IC and total factor productivity. Finally, it is suggested that the regulatory authorities advance digital infrastructure construction, to reinforce IC and risk prevention, thereby increase total factor productivity. And enterprises grasp the opportunity of digital economy development, promote the mechanism that digital transformation facilitates IC effectiveness, and increases total factor productivity. Non-high-tech ones motivate digital elements' governance efficacy, optimize executive structure, coordinately promote digital strategy, and help the national economy acquire high-quality development. The study provides enlightenments to achieve high-quality development.

Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis.

The gene hypermethylated in cancer 1 (HIC1) is epigenetically inactivated, but not mutated, in cancer. Here we show that cooperative loss of Hic1 with p53, but not INK4a, yields distinct tumor phenotypes in mice. Germline deletion of one allele of each gene on the opposite chromosome yields breast and ovarian carcinomas and metastatic osteosarcomas with epigenetic inactivation of the wild-type Hic1 allele. Germline deletion of the two genes on the same chromosome results in earlier appearance and increased prevalence and aggressiveness of osteosarcomas with genetic deletion of both wild-type genes. In human osteosarcomas, hypermethylation of HIC1 is frequent only in tumors with p53 mutations. Our results indicate the importance of genes altered only through epigenetic mechanisms in cancer progression in conjunction with genetically modified tumor suppressor genes.

[Simultaneous quantitative analysis of four lignanoids in Schisandra chinensis by quantitative analysis of multi-components by single marker].

The aim of the study is to establish a new method of quality evaluation and validate its feasibilities by the simultaneous quantitative assay of four lignanoids in Schisandra chinensis. A new quality evaluation method, quantitative analysis of multi-components by single marker (QAMS), was established and validated with Schisandra chinensis. Four main lignanoids, schisandrin, schisantherin A, deoxyschizandrin and gamma-schizandrin, were selected as analytes and schisandrin as internal reference substance to evaluate the quality. Their contents in 13 different batches of samples, collected from different bathes, were determined by both external standard method and QAMS. The method was evaluated by comparison of the quantitative results between external standard method and QAMS. No significant differences were found in the quantitative results of four lignanoids in 13 batches of S. chinensis determined by external standard method and QAMS. QAMS is feasible for determination of four lignanoids simultaneously when some authentic standard substances were unavailable, and the developed method can be used for quality control of S. chinensis.

[Simultaneous determination of eight iridoid glycosides in Gardeniae fructus by HPLC].

OBJECTIVE: To establish an HPLC method for simultaneous determination of eight iridiods in Gardeniae Fructus. METHOD: Kromasil C18 column (4. 6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-water-trifluoroacetic acid (6:94: 0.05) as the mobile phase at the flow rate of 1.0 mL x min(-1). The detection wavelength was set at 238 nm, and the column temperature was 40 degrees C. RESULT: The linear ranges of geniposide, gardoside, shanzhiside, geniposidic acid, deacetyl asperulosidic acid methyl ester, gardenoside, scandoside methyl ester, and genipin gentiobioside were 1.5036 - 15.036, 0.04256 - 0.4256, 0.1038 - 1.038, 0.00992 - 0.0992, 0.02332 - 0.2332, 0.4128 - 4.128, 0.02040 - 0.2040 and 0.4656 - 4.656 microg, respectively. Their average recoveries were 99.6% , 100.6% , 101.2%, 99.5%, 100.3% , 98.7%, 99.8% and 100.1%, respectively. CONCLUSION: The method shows good separation and it is so simple, accurate and highly repeatable that it can be used for providing basis for quality control of Gardeniae Fructus.

Corporate internal control, financial mismatch mitigation and innovation performance.

Based on the resource allocation optimization theory, from the perspective of internal control (IC) and financial mismatch jointly affecting technological innovation, this study selects the listed enterprises in China's capital market from 2012 to 2020 as the sample, and explores the mechanism among IC, financial mismatch and technological innovation. The results show that effective IC significantly promotes corporate innovation, and mitigates financial mismatch. The mitigation of financial mismatch presents a significant mediating effect between effective IC and innovation output. In Discussion, this study finds that the effects are significantly reflected in non-state-owned enterprises, but not in state-owned enterprises. Finally, it is suggested to improve IC effectiveness continuously, to stimulate innovation vitality, optimize financial resources allocation, and foster new momentum for economic development. And it is suggested to facilitate the transmission effect that effective IC mitigates financial mismatch, and enhances innovation output. Also, the innovation activities in state-owned and non-state-owned enterprises should be coordinated to promote the steady and healthy development of the economy.

Simultaneous elimination of amoxicillin and antibiotic resistance genes in activated sludge process: Contributions of easy-to-biodegrade food.

Antibiotics are continuously released into aquatic environments and ecosystems where they accumulate, which increases risks from the transmission of antibiotic resistance genes (ARGs). However, it is difficult to completely remove antibiotics by conventional biological methods, and during such treatment, ARGs may spread via the activated sludge process. Easy-to-biodegrade food have been reported to improve the removal of toxic pollutants, and therefore, this study investigated whether such co-substrates may also decrease the abundance of ARGs and their transferal. This study investigated amoxicillin (AMO) degradation using 0-100 mg/L acetate sodium as co-substrate in a sequencing biological reactor. Proteobacteria, Bacteroidetes, and Actinobacteria were identified as dominant phyla for AMO removal and mineralization. Furthermore, acetate addition increased the abundances of adeF and mdsC as efflux resistance genes, which improved microbial resistance, the coping ability of AMO toxicity, and the repair of the damage from AMO. As a result, acetate addition contributed to almost 100% AMO removal and stabilized the chemical oxygen demand (~20 mg/L) in effluents when the influent AMO fluctuated from 20 to 100 mg/L. Moreover, the total abundance of ARGs decreased by approximately ~30%, and the proportion of the most dominant antibiotic resistance bacteria Proteobacteria decreased by ~9%. The total abundance of plasmids that encode ARGs decreased by as much as ~30%, implying that the ARG spreading risks were alleviated. In summary, easy-to-biodegrade food contributed to the simultaneous elimination of antibiotics and ARGs in an activated sludge process.

[Covalent organic framework functional materials and their applications in glycopeptide enrichment].

Protein glycosylation is among the most important post-translational modifications in living organisms and the research in the field of protein glycosylation continues to garner attention. Currently, the efficient separation and enrichment of glycoproteins and glycopeptides is the primary challenge of glycoproteomics research. The number of glycoproteins is small in complex biological samples. Moreover, the presence of highly-abundant, non-glycosylated, and modified peptides makes the detection of low-abundance glycopeptides more difficult. Therefore, efficient glycopeptide enrichment methods are required to improve the detection of these compounds. The development of highly selective glycopeptide enrichment tools is important to efficiently capture glycoproteins or glycopeptides at the molecular level. Compared with traditional glycopeptide-enriched materials, covalent organic framework materials have the advantages of large specific surface area and rich modification sites, thereby exhibiting great application potential in the field of glycopeptide enrichment. In this study, a novel covalent organic framework material (O-T-D-COFs) was prepared and applied for selective glycopeptide enrichment. We applied the solvothermal method, using 2,5-dimethoxy benzene-1,4-2 formaldehyde and 1,3,5-Tris(4-aminophenyl) benzene, to synthesize imino-based COFs. The Schiff base generated via copolymerization condensation reaction constitutes the framework of the material. Next, the synthesized intermediate material was oxidized to improve the enrichment performance of the material. The functional, specific glycopeptide-binding groups were modified on the COF channels and the structure of the material was characterized using scanning and transmission electron microscope, as well as infrared spectrum and solid-state nuclear magnetic resonance. The enrichment conditions comprised the loading and elution steps, including the optimization of the elution conditions. We could observe the clear profile of 32 glycopeptides derived from human serum immunoglobulin G (IgG) tryptic digests with a significantly improved signal-to-noise (S/N) ratio. We applied a complex sample system to verify the enrichment selectivity of the material when the molar ratios of the IgG and bovine serum albumin (BSA) tryptic digest mixtures reached 1∶50. In addition, we investigated the enrichment performance of the detection limit, enrichment capacity, recovery rate of the material, and the application potential in glycopeptides enrichment using real samples. The material showed a good detection limit (2.5 fmol/µL), an ideal enrichment capacity (120 mg/g), and enrichment recovery (103.5%±6.6% and 101.5%±10.4%). We identified a total of 86 glycopeptides derived from 53 glycoproteins with 94 N-glycosylation sites from only 1 µL human serum. The O-T-D-COFs exhibited a good glycopeptide separation and enrichment potential, indicating that the COF material has promising application potential in glycoproteomics.

[Identification and analysis of an actinomycete strain suppressing Clavibacter michiganensis subsp, michiganensis].

OBJECTIVE: To identify and analyze bioactive compounds of an actinomycete strain Z-L-22 suppressing Clavibacter michiganensis subsp. michiganensis, the causal agent of bacterial canker of tomato. METHODS: Morphological, biological and biochemical characterization, chemotaxonomy analysis and 16S rDNA sequences homology analysis were performed to identify the strain Z-L-22. Bioactive compounds were separated and retrieved by thin layer chromatography. Paper chromatography and confirmation tests were used to identify the antibiotic. PCR was carried out using the primers targeted to synthetase of the antibiotic. RESULTS: Strain Z-L-22 belonged to Streptomyces sp. and was similar to Streptomyces setonii. Two main bioactive components were isolated by thin layer chromatography, which were all identified as actinomycin. New actinomycin synthetase gene was cloned using the primers designed from actinomycin synthetase conserve domain. CONCLUSION: Strain Z-L-22 was classified as Streptomyces setonii. Actinomycin produced by Streptomyces setonii was first reported.

Design of ruthenium-albumin hydrogel for cancer therapeutics and luminescent imaging.

Improving cell uptake of metal compounds has became an important goal in the field of metal-based anticancer agents. This may combat platinum resistance and side effects seen commonly in current anticancer chemotherapy regimes. Here, we explore a novel degradable ruthenium-albumin hydrogel, which shows strong luminescence for cell imaging and high selectivity for cancer cells versus non-cancer cells. This is an early indication of the possibility of reducing unwanted side effects of metals by using bovine serum albumin hydrogel as a delivery strategy. This work provides a strong basis for development of a new class of metal-based cancer therapeutic agents.

Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.

PURPOSE: EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. PATIENTS AND METHODS: We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively. RESULTS: Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases. CONCLUSION: Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.

Absence of a telomere maintenance mechanism as a favorable prognostic factor in patients with osteosarcoma.

There are two telomere maintenance mechanisms (TMMs) in human tumors, telomerase activation (TA) and, more rarely, the process termed alternative lengthening of telomeres (ALT). Unlike most carcinomas, sarcomas, including osteosarcomas (OS), have been reported to display TA and ALT in more balanced proportions and, thus, present an opportunity to examine the impact of different TMMs on clinical tumor behavior. We studied OS samples from 62 patients for molecular evidence of TA and ALT. Kaplan-Meier analysis demonstrated that the absence of both TA and ALT (in 18%) was more strongly associated with improved survival (P = 0.05) than were stage (P = 0.16) or chemotherapy response (P = 0.18) in this group of patients with OS. Subsets of OS cases with either TA or ALT did not differ significantly from each other in clinical outcome. There were no significant associations of presence, absence, or type of TMM with patient age, stage, or chemotherapy response. Thus, the absence of a detectable TMM may identify a favorable clinical subset of OS patients. Our study also suggests that the likelihood of detecting correlations between TMMs and clinical outcome in studies of certain other tumor types might be improved if, in addition to TA, ALT is included in future analyses. Finally, we note that OS cases with a TA-/ALT+ phenotype seem to be as clinically aggressive as TA+ cases in terms of stage and clinical outcome.

Effect of erythromycin on gastric dysmotility and neuroendocrine peptides in rats with diabetes mellitus.

OBJECTIVE: To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin (SS), vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP) in plasma and isolated gastric antrum tissue of diabetes mellitus (DM) rat models. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: control group (n = 10), DM group (n = 10), and erythromycin group (DM models with erythromycin treatment, n = 10). A single dose of streptozotocin (100 mg/kg, dissolved in 0.1 mol/L citric acid buffer, pH4.5) was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be (+++) to (++++) over one week were considered successful DM models. The resting tension, mean contractile amplitude and frequency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. RESULTS: (1) In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile frequency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension (P < 0.01). (2) Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control (P < 0.05), while the SP level decreased (P < 0.05). In the gastric antrum, SS of DM group was significantly higher than that of control group (P < 0.01), while SP and MTL levels were lower than those of control group (P < 0.05 and P < 0.01, respectively). However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group (P < 0.05). (3) The blood glucose was lower in erythromycin group than DM group (P < 0.01). CONCLUSIONS: Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia. The pathological hallmarks of AD are amyloid plaques [aggregates of amyloid-beta (Aß)] and neurofibrillary tangles (aggregates of tau). Growing evidence suggests that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than Aß plaques. Oxidative stress is a prominent early event in the pathogenesis of AD and is therefore believed to contribute to tau hyperphosphorylation. Several studies have shown that the autophagic pathway in neurons is important under physiological and pathological conditions. Therefore, this pathway plays a crucial role for the degradation of endogenous soluble tau. However, the relationship between oxidative stress, tau protein hyperphosphorylation, autophagy dysregulation, and neuronal cell death in AD remains unclear. Here, we review the latest progress in AD, with a special emphasis on oxidative stress, tau hyperphosphorylation, and autophagy. We also discuss the relationship of these three factors in AD.

Enhancement of osteopontin expression in HepG2 cells by epidermal growth factor via phosphatidylinositol 3-kinase signaling pathway.

AIM: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. It is unclear how osteopontin is regulated in HepG2 cells. The aim of this study was to investigate the effect of epidermal growth factor on the expression of osteopontin in HepG2 cells, and to explore the signal transduction pathway mediated this expression. METHODS: Osteopontin expression was detected by RNAase protection assay and Western blot. Wortmannin, a specific inhibitor of PI3K, was used to see if PI3K signal transduction was involved in the induction of osteopontin gene expression. RESULTS: HepG2 cells constitutively expressed low levels of osteopontin. Treatment with epidermal growth factor increased osteopontin mRNA and protein level in a dose- and time-dependent manner. Application of wortmannin caused a dramatic reduction of epidermal growth factor-induced osteopontin expression. CONCLUSION: Osteopontin gene expression can be induced by treatment of HepG2 cells with epidermal growth factor. Epidermal growth factor may regulate osteopontin gene expression through PI3K signaling pathway. Several potential targets in the pathway can be manipulated to block the synthesis of osteopontin and inhibit liver cancer metastasis.

Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases.

AIM: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (H pylori) as a risk factor for gastric cancer. METHODS: One hundred and seventy-one gastric samples were studied to detect telomerase activity using a telomerase polymerase chain reaction enzyme linked immunosorbent assay (PCR-ELISA), and c-Myc expression using immunohistochemistry. RESULTS: The telomerase activity and c-Myc expression were higher in cancers (87.69% and 61.54%) than in noncancerous tissues. They were higher in chronic atrophic gastritis with severe intestinal metaplasia (52.38% and 47.62%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.33% and 16.67%). In chronic atrophic gastritis with severe intestinal metaplasia, the telomerase activity and c-Myc expression were higher in cases with H pylori infection (67.86% and 67.86%) than in those without infection (21.43% and 7.14%). c-Myc expression was higher in gastric cancer with H pylori infection (77.27%) than in that without infection (28.57%). The telomerase activity and c-Myc expression were coordinately up-regulated in H pylori infected gastric cancer and chronic atrophic gastritis with severe intestinal metaplasia. CONCLUSION: H pylori infection may influence both telomerase activity and c-Myc expression in gastric diseases, especially in chronic atrophic gastritis.

Expression of COX-2 proteins in gastric mucosal lesions.

AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions and to assess the relationship between COX-2 expression and type, pathologic stage, differentiation, or lymph node metastasis in gastric cancer and the relationship between COX-2 expression and H pylori infection in gastric mucosal lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical resection. Samples were taken from tumor site and paracancerous tissues, and ABC immunohistochemical staining was used to detect the expression of COX-2 proteins. H pylori was determined by rapid urea test combined with pathological stating/14C urea breath test. RESULTS: The positive rate and staining intensity of mutant COX-2 gene expression in gastric cancer were significantly higher than those in paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant correlation between COX-2 and pathologic stage or lymph node metastasis type of gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was found between COX-2 expression and type or grade of differentiation (P>0.05). COX-2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%, 60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large proportion of gastric cancer tissues compared with matched non-cancerous tissues and was significantly associated with advanced tumor stage and lymph node metastasis. Overexpression of COX-2 plays an important role in tumor progression of gastric cancer. COX-2 may also play a role in the early development/promotion of gastric carcinoma and is associated with H pylori infection.

[Coordinated expression of c-Myc and telomerase activity in Helicobacter pylori infected gastric diseases].

OBJECTIVE: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (Hp) as a risk factor for gastric cancer. METHODS: 171 gastric samples were studied to detect telomerase activity with telomerase polymerase chain reaction enzyme linked immunosorbent assay and c-Myc expression using immunohistochemistry. RESULTS: Telomerase activity and c-Myc expression were higher in cancers (87.7% and 61.5%) than in noncancerous tissues. Telomerase activity and c-Myc expression were higher in chronic atrophic gastritis with moderate or severe intestinal metaplasia (52.4% and 47.6%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.3% and 16.7%). In chronic atrophic gastritis with moderate or severe intestinal metaplasia, telomerase activity and c-Myc expression were higher in cases with Hp infection (67.9% and 67.9%) than in these without infection (21.4% and 7.1%). c-Myc expression was higher in gastric cancer with Hp infection (77.3%) than that without infection (28.6%). Telomerase activity and c-Myc expression were coordinately up-regulated in Hp infected gastric cancer and chronic atrophic gastritis with moderate or severe intestinal metaplasia. CONCLUSIONS: Hp infection may influence both c-Myc expression and telomerase activity in gastric diseases, especially in chronic atrophic gastritis. c-Myc and telomerase co-expressed in gastric cancer and chronic atrophic gastritis with moderate or severe intestinal metaplasia.

[EGF/PI3K signaling pathway regulates the expression of osteopontin in liver cancer HepG2 cells].

OBJECTIVE: To investigate the effect of epidermal growth factor (EGF) on the expression of osteopontin (OPN) in liver cancer HepG2 cells. METHODS: Human liver caner cells of HepG2 line were cultured in medium without bovine serum. EGF was added. Another cells were pretreated with specific phosphatidylinositol 3 (PI3) inhibitor Wortmannin and then added with EGF. HepG2 cell were collected. RNase prote4ction assay and Western blotting were used to examine the expression of OPN in the HepG2 cells. RESULTS: HepG2 cells cultured in the bovine serum free medium expressed very low level of OPN. EGF increased the expression of OPN mRNA and protein in a dose- and time-dependent manners. Pretreatment of Wortmannin significantly reduced the EGF-induced OPN expression. CONCLUSION: EGF increases the OPN expression, possibly through PI3 signaling pathway. It is possible to block the synthesis of OPN through manipulating several target genes, thus inhibiting the metastasis of liver cancer.