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Biomedical subjects

Lin Li

Publications and source records attributed to Lin Li.

At least 109 records · Page 6Linked to original sources
PubMed2005

Reduction of PTP1B by RNAi upregulates the activity of insulin controlled fatty acid synthase promoter.

Metabolic deregulation accompanying type II diabetes is characterized by insulin resistance in peripheral tissues (liver, muscle, and adipose), mediated by impairments in insulin receptor (IR) signaling. Protein tyrosine phosphatase 1B (PTP1B) has been shown to be a negative regulator of IR autophosphorylation and thus has been considered as a major therapeutic target for the treatment of type II diabetes. We use RNA interference technique to downregulate PTP1B expression in hepatoma cell line. A secretory HBV s-antigen was introduced as reporter and driven by mouse fatty acid synthase promoter, which is positively controlled by insulin signaling. Liver-targeted hydrodynamic injection in tail vein was introduced to transfer siRNA (or siRNA expression vector) and reporter plasmid into mouse liver. On fasted/refed and glucose stimulation condition, the HBV s-antigen in sera in RNAi group was higher than that in the negative group. Our results provided evidence that upregulation of insulin signaling by reducing PTP1B liver with RNAi can be a potent diabetes treatment method.

Animals↗
PubMed2005

Regulation of PTEN by Rho small GTPases.

PTEN (phosphatase and tensin homologue) is a phosphatase that dephosphorylates both protein and phosphoinositide substrates. It is mutated in a variety of human tumours and has important roles in a diverse range of biological processes, including cell migration and chemotaxis. PTEN's intracellular localization and presumably activity are regulated by chemoattractants in Dictyostelium and mouse neutrophils. However, the mechanisms for its regulation remain elusive. Here we show that RhoA and Cdc42, members of the Rho family of small GTPases, regulate the intracellular localization of PTEN in leukocytes and human transfected embryonic kidney cells. In addition, active RhoA is able to stimulate the phospholipid phosphatase activity of PTEN in human embryonic kidney cells and leukocytes, and this regulation seems to require RhoA's downstream effector, RhoA-associated kinase (Rock). Furthermore, we have identified key residues on PTEN that are required for its regulation by the small GTPase, and show that small GTPase-mediated regulation of PTEN has a significant role in the regulation of chemotaxis.

Animals↗
PubMed2005

Optimized normalization for antibody microarrays and application to serum-protein profiling.

The measurements of coordinated patterns of protein abundance using antibody microarrays could be used to gain insight into disease biology and to probe the use of combinations of proteins for disease classification. The correct use and interpretation of antibody microarray data requires proper normalization of the data, which has not yet been systematically studied. Therefore we undertook a study to determine the optimal normalization of data from antibody microarray profiling of proteins in human serum specimens. Forty-three serum samples collected from patients with pancreatic cancer and from control subjects were probed in triplicate on microarrays containing 48 different antibodies, using a direct labeling, two-color comparative fluorescence detection format. Seven different normalization methods representing major classes of normalization for antibody microarray data were compared by their effects on reproducibility, accuracy, and trends in the data set. Normalization with ELISA-determined concentrations of IgM resulted in the most accurate, reproducible, and reliable data. The other normalization methods were deficient in at least one of the criteria. Multiparametric classification of the samples based on the combined measurement of seven of the proteins demonstrated the potential for increased classification accuracy compared with the use of individual measurements. This study establishes reliable normalization for antibody microarray data, criteria for assessing normalization performance, and the capability of antibody microarrays for serum-protein profiling and multiparametric sample classification.

Adenocarcinoma↗
PubMed2005

SDS-aided immobilization and controlled release of camptothecin from agarose hydrogel.

Camptothecin (CPT), known to be an effective anticancer drug, has a limited therapeutic utility because of its poor water solubility. In this work, an approach has been made to overcome the limitation. CPT was first incorporated into the micelles formed from an ionic surfactant, sodium dodecyl sulfate (SDS) and the micellar drug aqueous solution was then used in preparation of the agarose hydrogel. It has been found that the presence of SDS greatly increased the solubility of CPT in water. For example, in 1 ml of 1.0 wt.% SDS water solution, 0.11 mg CPT could be solubilized (0.318 mM), which was 83 times the solubility in pure water. It was the hydrophobic cores of the SDS micelles that were able to accept the lipophilic drug to form stable drug-immobilized micelles. The formulation of a hydrogel using the drug-immobilized micelles has allowed us to obtain a unique and novel drug release system where the drug molecules are encapsulated by the micelles and the drug-containing micelles are dispersed in the gel network. The release of CPT from the so deliberately fabricated agarose hydrogel system has been studied as a function of surfactant concentration at 37 degrees C. The diffusion coefficients of CPT obtained by fitting to Fick's law ranged from 2.12 to 7.36 x 10(-7)cm(2)s(-1). The results showed that SDS prolonged the drug release by reducing the diffusion coefficient of CPT in the gel.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Mutation analysis of autosomal dominant polycystic kidney disease genes in Han Chinese.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2. The complexity of these genes, particularly PKD1, has complicated genetic screening, though recent advances have provided new opportunities for amplifying these genes. In the Han Chinese population, no complete mutational analysis has previously been conducted across the entire span of PKD1 and PKD2. Here, we used single-strand conformation polymorphism (SSCP) analysis to screen the entire coding sequence of PKD1 and PKD2 in 85 healthy controls and 72 Han Chinese from 24 ADPKD pedigrees. In addition to 11 normal variants, we identified 17 mutations (12 in PKD1 and 5 in PKD2), 15 of which were novel ones (11 for PKD1 and 4 for PKD2). We did not identify any seeming mutational hot spots in PKD1 and PKD2. Notably, we found several disease-associated C-T or G-A mutations that led to charge or hydrophobicity changes in the corresponding amino acids. This suggests that the mutations cause conformational alterations in the PKD1 and PKD2 protein products that may impact the normal protein functions. Our study is the first report of screenable mutations in the full-length PKD1 and PKD2 genes of the Han Chinese, and also offers a benchmark for comparisons between Caucasian and Han ADPKD pedigrees and patients.

Adult↗
PubMed2005

Cost-effective method of siRNA preparation and its application to inhibit hepatitis B virus replication in HepG2 cells.

AIM: To find a cost-effective method of preparation of short interfering RNAs based on cloning, fermentation, digestion and purification (CFDP) and test its feasibility to inhibit hepatitis B virus replication in cell culture. METHODS: We constructed an expression vector containing T7 and tac promoter in a head-to-head orientation. cDNA fragment of interest was cloned into this vector between the opposing promoters. dsRNAs were expressed with this vector in Escherichia coli, and purified by affinity chromatography using CF 11 column. They were digested by RNase III in a buffer containing manganese ions, then separated on 15% non-denaturing PAGE, and the siRNAs about 25 bp in length were recovered. siRNAs prepared with CFDP were co-transfected with target gene expression plasmid into human cell lines with lipofectamine 2,000 to test their inhibition efficiency. RESULTS: siRNAs corresponding to part of the hepatitis B virus polymerase gene (siHBVP) prepared by CFDP specifically and dramatically suppressed the virus protein expression. The HBsAg expression level was reduced to 10% that of the control by co-transfection of 60 nmol/L siHBVP in SMMC7721 cells. Dose-dependent effect on suppression of HBsAg and HBeAg expression was observed in HepG2 cells. The highest inhibition rate was kept at 70% during the six days after transfection of 7.5 nmol/L siHBVP. CONCLUSION: We show CFDP is a very promising method to prepare therapeutic agents in anti-virus applications.

Base Sequence↗
PubMed2005

Behavioural study of the D-galactose induced aging model in C57BL/6J mice.

Rodent chronically injected with D-galactose (D-gal) has been used as an animal aging model for brain aging or anti-aging pharmacology research. However, the dosage of D-gal used to establish this model in mice has been reported in a wide range. To study the dose-dependent effect of D-gal on rodent behaviour, we investigated the learning and memory ability of C57BL/6J (C57) mice after 8-week subcutaneous injection of D-gal at different doses by Morris water maze (MWM) and object recognition test (ORT). In addition, locomotor activity test (LAT) was also performed to examine the neuromuscular function. In comparison of vehicle (0.9% saline)-treated mice, D-gal-treated mice at dose of high (200 mg/kg per day) and middle (100 mg/kg per day) doses showed significant longer latency to platform and less target quadrant search time and distance in MWM In ORT, D-gal at high and middle doses reduced the discrimination index (DI) of mice more significantly than low dose (50 mg/kg per day), although all three doses of D-gal reduced the DI of mice significantly. Furthermore, D-gal at high and middle doses significantly decreased locomotor activity of the mice in LAT. Throughout three tests, D-gal induced behavioural impairments in C57 mice at high and middle doses tended to be in the same degree. These results indicate that d-gal can induce the behavioural impairment of C57 mice in a dose-dependent manner from 50 to 100 mg/kg, higher dose than 100 mg/kg cannot further deteriorate its behavioural performance.

Aging↗
PubMed2005

Estrogen regulation of trefoil factor 1 expression by estrogen receptor alpha and Sp proteins.

Estrogen-responsive genes in human breast cancer cells often have an estrogen response element (ERE) positioned next to an Sp1 binding site. In chromatin immunoprecipitation (ChIP) assays, we investigated the binding of estrogen receptor alpha (ER), Sp1, and Sp3 to the episomal and native estrogen-responsive trefoil factor 1 (TFF1; formerly pS2) promoter in MCF-7 breast cancer cells. Mutation of the Sp site upstream of the ERE reduced estrogen responsiveness and prevented binding of Sp1 and Sp3, but not ER to the episomal promoter. In the absence of estradiol (E2), Sp1, Sp3, histone deacetylase 1 (HDAC), and HDAC2, and low levels of acetylated H3 and H4 are associated with the native promoter, with the histones being engaged in dynamic reversible acetylation. Following E2 addition, levels of ER and acetylated H3 and H4 bound to the native promoter increases. There is clearance of Sp1, but not of Sp3, from the promoter while HDAC1 and HDAC2 remain bound. These data are consistent with a model in which Sp1 or Sp3 aid in recruitment of HDACs and histone acetyltransferases (HATs) to mediate dynamic acetylation of histones associated with the TFF1 promoter, which is in a state of readiness to respond to events occurring following the addition of estrogen.

Acetylation↗
PubMed2005

gp49B1 deficiency is associated with increases in cytokine and chemokine production and severity of proliferative synovitis induced by anti-type II collagen mAb.

Mice with a disrupted gp49B gene, which encodes gp49B1 that is expressed on certain hematopoietic cells and has two immunoreceptor tyrosine-based inhibitory motifs (ITIM), exhibit augmented FcepsilonRI-initiated mast cell degranulation and resultant tissue edema. gp49B1-deficient (gp49B(-/-)) mice also exhibit exaggerated lipopolysaccharide (LPS)-induced intravascular neutrophil aggregation leading to cutaneous microangiopathy. To determine whether gp49B(-/-) mice exhibit elevated cytokine and chemokine levels leading to pathologic inflammation, we quantified clinical and morphologic parameters of arthritis and tissue levels of contributory mediators in gp49B(-/-) and gp49B1-sufficient (gp49B(+/+)) mice injected with anti-type II collagen monoclonal antibody (mAb) and LPS. Clinical scores for joint swelling and histological assessments of synovial thickness and cartilage matrix depletion at day 7 were significantly 2.3- to 2.5-fold greater and were more prolonged in gp49B(-/-) mice. At day 5, the amounts of IL-1beta, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were 2.1-, 2.5-, and 12-fold greater in joint extracts from gp49B(-/-) mice. A significant 2.7-fold more neutrophils infiltrated the synovium of gp49B(-/-) mice at day 7, and neutrophilia persisted with the delayed resolution of the synovitis. mAb-mediated depletion of neutrophils prevented the synovitis in both strains. Thus, gp49B1 counter-regulates the cytokine and chemokine induction and attendant neutrophilia that are all essential for synovitis and cartilage matrix depletion.

Animals↗
PubMed2005

Hepatitis B awareness, testing, and knowledge among Vietnamese American men and women.

Southeast Asians have higher rates of liver cancer than any other racial/ethnic group in the United States. Chronic carriage of hepatitis B virus (HBV) is the most common underlying cause of liver cancer in the majority of Asian populations. Our objectives were to describe Vietnamese Americans' awareness of hepatitis B, levels of HBV testing, and knowledge about hepatitis B transmission; and to compare the HBV knowledge and practices of men and women. A community-based, in-person survey of Vietnamese men and women was conducted in Seattle during 2002. Seven hundred and fifteen individuals (345 men and 370 women) completed the questionnaire. Eighty-one percent of the respondents had heard of hepatitis B (76% of men, 86% of women) and 67% reported HBV testing (66% of men, 68% of women). A majority of the participants knew that HBV can be transmitted during sexual intercourse (71% of men, 68% of women), by sharing toothbrushes (67% of men, 77% of women), and by sharing razors (59% of men, 67% of women). Less than one-half knew that hepatitis B is not spread by eating food prepared by an infected person (46% of men, 27% of women), nor by coughing (39% of men, 25% of women). One-third of our respondents did not recall being tested for HBV. Important knowledge deficits about routes of hepatitis B transmission were identified. Continued efforts should be made to develop and implement hepatitis B educational campaigns for Vietnamese immigrant communities. These efforts might be tailored to male and female audiences.

Adult↗
PubMed2005

5-year urinary and sexual outcomes after radical prostatectomy: results from the prostate cancer outcomes study.

PURPOSE: Prior studies of postoperative outcomes following radical prostatectomy have been limited by selection bias and short-term followup. In this study we assessed temporal changes in urinary and sexual function up to 5 years following radical prostatectomy in a population based cohort. MATERIALS AND METHODS: A sample of 1,288 men with localized prostate cancer who underwent radical prostatectomy and completed a baseline survey within 6 to 12 months of diagnosis were included in the analysis. Two and 5-year functional and quality of life data were collected, as was information on the use of erectile aids. Temporal functional changes and potentially confounding or modifying factors were assessed using longitudinal regression models. RESULTS: Of these men 14% reported frequent urinary leakage or no urinary control 60 months after diagnosis, which was slightly higher than the 10% reporting incontinence at 24 months (p = 0.007). At 60 months 28% of the men had erections firm enough for intercourse compared with 22% at 24 months (p = 0.003). Sildenafil was the most commonly used erectile aid (43% ever used) and 45% of users reported that it helped "somewhat" or "a lot." CONCLUSIONS: Urinary and sexual dysfunction were common 5 years following radical prostatectomy in this large, community based cohort of prostate cancer survivors. While a small minority of subjects experienced changes in urinary or sexual function between years 2 and 5 after prostatectomy, functional outcomes remained relatively stable in the majority of participants.

Adult↗
PubMed2005

A microarray analysis of the rice transcriptome and its comparison to Arabidopsis.

Arabidopsis and rice are the only two model plants whose finished phase genome sequence has been completed. Here we report the construction of an oligomer microarray based on the presently known and predicted gene models in the rice genome. This microarray was used to analyze the transcriptional activity of the gene models in representative rice organ types. Expression of 86% of the 41,754 known and predicted gene models was detected. A significant fraction of these expressed gene models are organized into chromosomal regions, about 100 kb in length, that exhibit a coexpression pattern. Compared with similar genome-wide surveys of the Arabidopsis transcriptome, our results indicate that similar proportions of the two genomes are expressed in their corresponding organ types. A large percentage of the rice gene models that lack significant Arabidopsis homologs are expressed. Furthermore, the expression patterns of rice and Arabidopsis best-matched homologous genes in distinct functional groups indicate dramatic differences in their degree of conservation between the two species. Thus, this initial comparative analysis reveals some basic similarities and differences between the Arabidopsis and rice transcriptomes.

Arabidopsis↗
PubMed2005

The neuroplasticity-associated arc gene is a direct transcriptional target of early growth response (Egr) transcription factors.

Early growth response (Egr) transcription factors (Egr1 to Egr4) are synaptic activity-inducible immediate early genes (IEGs) that regulate some aspects of synaptic plasticity-related to learning and memory, yet the target genes regulated by them are unknown. In particular, Egr1 is essential for persistence of late-phase long-term potentiation (L-LTP), for hippocampus-dependent long-term memory formation, and for reconsolidation of previously established memories. Here, we show that Egr1 and Egr3 directly regulate the plasticity-associated activity-regulated cytoskeletal-related (Arc) gene, a synaptic activity-induced effector molecule which is also required for L-LTP and hippocampus-dependent learning and memory processing. Moreover, Egr1-deficient and Egr3-deficient mice lack Arc protein in a subpopulation of neurons, while mice lacking both Egr1 and Egr3 lack Arc in all neurons. Thus, Egr1 and Egr3 can indirectly modulate synaptic plasticity by directly regulating Arc and the plasticity mechanisms it mediates in recently activated synapses.

Animals↗
PubMed2005

[Discussion of some problems in studying relationship between sphygmo-diagram and syndrome types or diseases].

In contemporary studies of pulse and of the relationship between sphygmo-diagram and syndrome types or diseases, pulse instrument is usually applied to trace the sphygmo-diagram. A comparatively systemic theory about pulse diagnosis has been formed, and it promotes the pulse researching process. But the mechanism of pulse is complicated and the expressive information of pulse is diversity. So it is difficult to record the complicated information of pulse by applying the instrument. In addition, the simplicity in methods of tracing and analyzing sphygmo-diagram and the lack of criterion for syndrome differentiation make it difficult to study the relationship between the sphygmo-diagram and the syndrome types. It's important to lay stress on clinical applying, to promote communication among researchers, to unify the standards of pulse instrument and syndrome differentiation, and to reinforce the research on the relationship between sphygmo-diagram and the syndrome types. The government's support is also needed to promote multi-science cooperation at the same time.

Diagnosis, Differential↗
PubMed2005

[Effects of ginkgolide on cerebral blood flow in dogs].

OBJECTIVE: To observe the effects of ginkgolide (GL) on the cerebral blood flow in dogs. METHODS: Dogs anesthetized with sodium pentobarbital were randomly divided into 5 groups, with 4 dogs in each group. Ginkgolide of 4.86, 14.6 and 43.7 mg/kg and Xingling Granule of 0.22 g/kg were administered by gavage to the dogs in each of 4 groups. The dogs in the other group were administered with edible oil (1 ml/kg) as control group. The cerebral blood flow, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and electro-cardiogram of the dogs were measured at different times after the administration. RESULTS: Ginkgolide of 4.86, 14.6 and 43.7 mg/kg had no obvious effects on the blood pressure and the heart rate. Ginkgolide of 14.6 and 43.7 mg/kg increased the cerebral blood flow 90 minutes after administration, and ginkgolide of 43.7 mg/kg obviously decreased the cerebral vascular resistance 150 minutes after administration. CONCLUSION: Ginkgolide can increase the cerebral blood flow and decrease the cerebral vascular resistance, and it has no obvious effects on blood pressure and heart rate in dogs.

Animals↗
PubMed2005

Sarcomatoid renal cell carcinoma with divergent sarcomatoid growth patterns: a case report and review of the literature.

A 71-year-old woman who presented with left abdominal pain was found to have a noncalcified renal mass with a perisplenic extension on imaging studies. Histologically, the tumor showed predominantly malignant spindle cells with extensive osteoid and chondroid matrix production. Various growth patterns resembling rhabdomyosarcoma, malignant fibrous histiocytoma, and fibrosarcoma were also observed. Immunohistochemistry showed positive staining of the neoplastic cells for cytokeratin and focally positive staining for CD10 and CD117 (c-Kit). Electron microscopic examination revealed a poorly differentiated neoplasm with both mesenchymal and epithelial features. The tumor was diagnosed as a sarcomatoid renal cell carcinoma with overgrowth of the sarcomatoid component (World Health Organization: renal cell carcinoma, unclassified). To our knowledge, sarcomatoid renal cell carcinoma with such a broad morphologic phenotype in a single case has not been documented. Furthermore, the CD117 expression in a sarcomatoid renal cell carcinoma that was observed in this case merits further investigation.

Aged↗