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Biomedical subjects

J J Liu

Publications and source records attributed to J J Liu.

At least 19 recordsLinked to original sources

Systemic lupus erythematosus: a genetic epidemiology study of 695 patients from China.

Our purpose was to explore potential genetic models for systemic lupus erythematosus (SLE) and analyze genetic epidemiologic characteristics of SLE in a Chinese population. Data for 695 patients with SLE were obtained by using a uniform questionnaire. Patients, clinical characteristics and their family history were analyzed using software. A complex segregation analysis was conducted to propose potential genetic models for SLE. The mean +/- SD age of onset were 30.2 +/- 10.5 years and mean time to progression to SLE was 32.5 +/- 44.4 months. The most frequent initial manifestations were malar rash (61.3%). During the evolution of the disease, the main clinical features were arthritis in 73.6% of our patients, followed by malar rash (68.1%), and renal involvement (56.7%). As the first symptom, the late-onset group (onset of disease beyond the age of 50 years) less often showed malar rash (45% vs. 63.4% in the early-onset group; p = 0.001). There were no significant differences in the other cumulative clinical symptoms between late-onset and early-onset group, except for a lower prevalence of malar rash, photosensitivity and alopecia and a higher prevalence of mucosal ulcers in the late-onset group. A positive family history of SLE was obtained in 50 patients (7.2%). There were no statistical differences in clinical characteristics between familial SLE and sporadic SLE patients. The heritability of SLE was 43.6%, the genetic model of SLE could be polygenetic model and major gene mode is the best fitted one. SLE could be a multifactorial disease with polygenetic model.

Adolescent↗

The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

Aged↗

A two-dimensional adsorption kinetic model for thermal hysteresis activity in antifreeze proteins.

Antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs), collectively abbreviated as AF(G)Ps, are synthesized by various organisms to enable their cells to survive in subzero environments. Although the AF(G)Ps are markedly diverse in structure, they all function by adsorbing to the surface of embryonic ice crystals to inhibit their growth. This adsorption results in a freezing temperature depression without an appreciable change in the melting temperature. The difference between the melting and freezing temperatures, termed thermal hysteresis (TH), is used to detect and quantify the antifreeze activity. Insights from crystallographic structures of a number of AFPs have led to a good understanding of the ice-protein interaction features. Computational studies have focused either on verifying a specific model of AFP-ice interaction or on understanding the protein-induced changes in the ice crystal morphology. In order to explain the origin of TH, we propose a novel two-dimensional adsorption kinetic model between AFPs and ice crystal surfaces. The validity of the model has been demonstrated by reproducing the TH curve on two different beta-helical AFPs upon increasing the protein concentration. In particular, this model is able to accommodate the change in the TH behavior observed experimentally when the size of the AFPs is increased systematically. Our results suggest that in addition to the specificity of the AFPs for the ice, the coverage of the AFPs on the ice surface is an equally necessary condition for their TH activity.

Adsorption↗

Optimization for quantitative determination of four flavonoids in Epimedium by capillary zone electrophoresis coupled with diode array detection using central composite design.

Herba Epimedii (family Berberidaceae), Ying-Yang-Huo in Chinese, is a famous Chinese herbal medicine. Flavonoids are thought to be the major active components in it. A capillary zone electrophoresis (CZE) separation were developed for simultaneous determination of four flavonoids including icariin, epimedin A, epimedin B and epimedin C in Epimedium. The effects of the experimental variables on CZE had been optimized by using central composite design (CCD). The best separation of four flavonoids could be obtained using 50 mM borate buffer (pH 10.0) containing 22% acetontrile as modifier, while separation voltage was 15 kV and temperature was at 25 degrees C. The method developed is accurate, simple and reproducible, which could be used for quality control of Epimedium and its medical preparations.

Electrochemistry↗

Analysis of LRRK2 functional domains in nondominant Parkinson disease.

A comprehensive sequence analysis of 29 exons that code for the functional domains of LRRK2 in 160 nondominant Parkinson disease (PD) patients was performed. Novel variant screening in a further 470 sporadic PD patients and 630 controls revealed two novel variants (R1067Q and IVS33 + 6 T>A), which are likely to be pathogenic in five patients. One patient presented initially with a typical essential tremor phenotype, expanding the phenotypic spectrum of LRRK2 mutations.

Adult↗

GC-MS fingerprint of Pogostemon cablin in China.

Pogostemon cablin, originating in Malaysia and India, is cultivated in southern China including Guangdong and Hainan Province, which was called GuangHuoXiang to differentiate it from the HuoXiang of the north, the species Agastache rugosa, that it resembles. Essential oil of P. cablin mainly contributes to the pharmacological activities and the therapeutic properties of the essential oils are directly correlated with their qualitative and quantitative composition. For controlling the quality, standard fingerprint of P. cablin collected from different regions was developed by using GC-MS. Nine compounds including beta-patchoulene, caryophyllene, alpha-guaiene, seychellene, beta-guaiene, delta-guaiene, spathulenol, patchouli alcohol and pogostone were identified among 10 main peaks in P. cablin. Hierarchical clustering analysis based on characteristics of 10 investigated peaks in GC profiles showed that 18 samples were divided into three main clusters, patchouliol-type, pogostone-type and an interim-type, which was the one between the two chemotypes. The simulative mean chromatogram for the three types P. cablin was generated using the Computer Aided Similarity Evaluation System. The fingerprint can help to distinguish the substitute or adulterant, and further assess the differences of P. cablin grown in various areas of China.

China↗

Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-gamma ligands induces apoptosis on human myeloid leukemia cells in vitro.

The present study was undertaken to investigate the mechanisms of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligand-induced apoptosis on human myeloid leukemia K562 and HL-60 cell lines. The results revealed that both 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) have significant anti-proliferation- and apoptosis-inducing effects on these two kinds of leukemia cells. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly using Wright's and Hoechst 33258 staining. Reverse transcription-PCR and western blot analyses demonstrated that both survivin and bcl-2 expression were downregulated markedly, while bax expression was upregulated concurrently when apoptosis occurred. We therefore conclude that 15d-PGJ2 and TGZ have significant apoptosis effects on K562 and HL-60 cells in vitro, and that upregulation of bax as well as downregulation of survivin and bcl-2 expression may be the important apoptosis-inducing mechanisms. The results suggest that PPAR-gamma ligands may serve as potential therapeutic agents for both acute and chronic myeloid leukemia.

Antineoplastic Agents↗

Analysis of factors affecting the epidemiology of tuberculosis in China.

SETTING: The tuberculosis (TB) epidemic situation is both a public health problem and a socio-economic issue in China. OBJECTIVE: To examine the effects of socio-economic development and of the TB control strategy on the TB epidemic in China. METHODS: Based on the four National Epidemiological Surveys of TB and the indices of socio-economic development in China, correlation co-efficiency was used to analyse the relationship between changes in the TB epidemic situation, the socio-economic level and the Health V TB control Project. RESULTS: The prevalence of smear-positive TB had significant medium correlation with the per capita net income of the rural population, the consumption level of the urban population, the per capita GDP, the population density, and the proportion of rural to total population, among which the correlation with the first four was negative and with the last was positive. The decline in prevalence in the project areas was much greater than in the non-project areas (44.4% vs. 12.3%), while their GDP increases were similar. CONCLUSION: With socio-economic development, correlation between the socio-economic indices and the TB epidemic becomes more significant. The TB control project is vital to reduce the prevalence of TB in China.

China↗

Oridonin-induced apoptosis in leukemia K562 cells and its mechanism.

Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Recently oridonin has been reported to have anti- tumor effects in a large variety of malignant diseases. In this study, we investigated the apoptotic inducing effect of oridonin in leukemia K562 cells and its mechanism. Cell growth inhibition was measured using a microculture tetrazolium assay, apoptosis was measured by flow cytometry and electron microscopy as well as by DNA fragmentation analysis. Telomerase activity was measured by TRAP-enzyme- linked immunosorbent assay, and the expression of Bcl-2 and Bax proteins was detected by western blot analysis. The results showed that oridonin could inhibit the proliferation and induce apoptosis on leukemia K562 cells remarkably. Telomerase activity as well as Bcl-2 expression was down- regulated, while Bax expression was up-regulated concurrently, when apoptosis ocurred. We therefore conclude that oridonin demonstrated anti-proliferative and apoptosis-inducing effects on K562 cells in vitro, and that changes in bcl-2 and bax protein levels as well as telomerase activity may play an important role in its mechanism of action.

Antineoplastic Agents↗

Simultaneous determination of six main nucleosides and bases in natural and cultured Cordyceps by capillary electrophoresis.

A simple method is described for simultaneous determination of six main nucleosides and bases including adenine, uracil, adenosine, guanosine, uridine and inosine in Cordyceps by capillary electrophoresis (CE). Chemometric optimization based on central composite design was employed to find the optimum resolution. The optimum factor space was defined by three parameters: buffer concentration, pH and concentration of acetonitrile as organic modifier. Resolution (Rs) was employed to evaluate the response function. A running buffer composed of 500 mM boric acid, adjusted pH to 8.6 with sodium hydroxide and 12.2% acetonitrile as modifier was found to be the most appropriate for the separation. The contents of the six components were determined by using adenosine monophosphate as an internal standard. Furthermore, hierarchical clustering analysis based on characteristics of 32 peaks in CE profiles from the tested 12 samples showed that natural and cultured Cordyceps were in different clusters. Adenosine and inosine were extracted as markers for discrimination of natural Cordyceps. The result of clustering based on the two peaks characteristics was in excellent agreement with that based on 32 peaks'. Thus, adenosine and inosine could be used as markers for quality control of natural and cultured Cordyceps.

Buffers↗

Endoluminal gastroplication for treatment of patients with classic gastroesophageal reflux symptoms and borderline 24-h pH studies.

BACKGROUND: Patients with classic gastroesophageal reflux disease (GERD) symptoms and borderline 24-h pH studies are not considered to be good candidates for surgical fundoplication. Endoluminal gastroplication (ELGP) is a new endoscopic treatment for patients with GERD. The aim of this study was to evaluate the efficacy of ELGP in these patients. METHODS: Patients with heartburn, regurgitation symptoms and a DeMeester score of less than 30 were studied. ELGP involved placement of two or three plications within 2 cm of the gastroesophageal junction. Clinical outcomes measured were heartburn symptom score (HSS), regurgitation frequency score (RFS) and medication use. RESULTS: Twenty-five patients (11 M, 14 F, mean age of 51 years) had a medication use of 11.5 doses of proton-pump inhibitors per week prior to ELGP. Average lower esophageal sphincter pressure measured 15 +/- 8 mmHg, and average DeMeester score was 18 +/- 8. Nine patients had hiatal hernias and 11 had esophagitis. Twenty-four patients were available for a mean follow-up of 12 months. HSS significantly decreased from 48 to 17 (P < 0.01) and RFS was reduced from 1.8 to 0.7 (P < 0.01). Proton-pump inhibitor use was 5.3 doses per week (P < 0.01) post-ELGP; 12 patients (50%) were off medications, 3 (13%) had a 50% reduction in medication use, and in 9 (37%) there was no change. Complications were bleeding in one patient and aspiration pneumonia in another patient. CONCLUSIONS: Endoluminal gastroplication provides symptomatic relief for patients with classic GERD symptoms despite medical therapy and borderline 24-h pH studies.

Adult↗

Cloning and sequencing of complete cDNA of Japanese encephalitis virus YL strain in Taiwan.

We determined the complete nucleotide sequence of the YL strain of Japanese encephalitis virus and its amino acid sequence was deduced. Our results displayed that the genome of YL strain contained a single open reading frame of 10,296 nucleotides (nts) which was flanked by untranslated region (UTR) containing 95 bases at the 5'-end and 586 bases at the 3'-end, respectively. Comparison of sequences showed that the overall amino acid sequence and 3' UTR of YL were similar to those of the virulent strain JaGAr0l. However, some significant amino acid differences of viral envelope (E) protein were observed between YL and JaGAr01; the amino acid sequence of E protein in YL strain possessed RGG(387-389) tripeptide instead of RGD(387-389) in JaGAr01 and in other strains; and another amino acid is K(138) in YL, not E(138) found in others. These differences suggested that the YL strain impairs in viral attachment to the cell surface and loses neuroinvasiveness, and therefore this strain was used as a live attenuated vaccine.

3' Untranslated Regions↗

Cloning and sequencing of full-length cDNA of classical swine fever virus LPC strain.

The cDNAs of classical swine fever virus (LPC vaccine strain) were cloned by transcriptase-polymerase chain reaction, and their nucleotide sequences were determined. In this work, we obtained the sequence information of the 786 bases of the 5'-terminal region, 6049 bases of the middle region, and 1648 bases of the 3'-terminal region. Taking our previous results and present data together, the entire genomic sequence of LPC strain was completed (12344 nucleotides in length). The genome of LPC has a large open reading frame that can encode a polypetide of 3897 amino acids, and are flanked by untranslated regions (UTR), 373 bases at the 5'-end and 278 bases at the 3'-end. Phylogenetic analysis based on genomic sequences of several viruses suggested that the LPC strain is closer to Chinese, Riems, HCLV, Alfort/187, Brescia, and Alfort strains in order. After further analysis, we found that an insertion of 13 nucleotides, TTT(C/T)CTTTTTTTT, in the 3'-UTR of LPC, Chinese, and HCLV strains. Immediately downstream to the 13 nucleotides, a unique sequence of LPC consisting of 28 thymidine was observed.

Base Sequence↗

Differential expression analysis by gene array of cell cycle modulators in human corneal epithelial cells stimulated with epidermal growth factor (EGF), hepatocyte growth factor (HGF), or keratinocyte growth factor (KGF).

PURPOSE: To identify and differentiate cell cycle and differentiation genes that are up-regulated or down-regulated in human corneal epithelial cells in response to alternative epithelium-modulating cytokines epidermal growth factor (EGF), hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF). METHODS: Primary cultures human corneal epithelial cell (HCE) were treated with 25 ng/ml of EGF, 25 ng/ml HGF, 25 ng/ml KGF, or vehicle for 8 hours. Complementary DNA (cDNA) probes were synthesized from total cellular RNA isolated from the HCE cells. The cDNA probes were hybridized to the Atlas human cell cycle/differentiation array membrane. RNAse protection assay was used to confirm up-regulation of the serine/threonine-protein kinase PITALRE gene by EGF, KGF, and HGF. RESULTS: The expression of one hundred and eleven cell cycle and differentiation genes was monitored with the gene array system. It was found that these epithelial cell-modulating cytokines shared similar effects on some of the cell cycle and differentiation genes that were monitored, but had specific effects on some cytokines. Up-regulation of PITALRE gene expression was confirmed using RNAse protection assay. CONCLUSION: EGF, HGF and KGF had differential effects on cell cycle- and differentiation-related gene expression in corneal epithelial cells. For example, all three mitogenic growth factors up-regulated the expression of cyclin D1 (BCL-1 oncogene) and serine/threonine-protein kinase PITALRE in the primary cultured human corneal epithelial cells. However, EGF and KGF, but not HGF, up-regulated expression of the E2F-1 pRB-binding protein gene. Thus, while these three epithelial mitogens have similar effects on many genes that were analyzed, important differences were noted that may relate to differing effects of these growth factors on corneal epithelial cells. Studies to analyze the significance of the identified differences among these growth factors are in progress.

Cell Cycle↗

[Research on the selecting suspension cell line of higher productivity of flavonol glycoside by hypoxia stress as well as the stability in subcultures].

Investigate the influence of culture media to growth and flavonol glycoside synthesis of calli introduced from seedling of Ginkgo biloba. 6 cell lines were selected from calli by hypoxia stress. Among these cell lines the best one TZ-1 which growth index was 4.12 and the flavonol glycoside content was 1.25% in dried cell which was enhanced 257.1% compared with callus. The stability in subcultures was investigated: The average content of flavonol glycoside was 1.25% in dried cells and the growth index was 3.99 during 6 subcultures. Which variation coefficient was separately 0.065 and 0.048. The results show that hypoxia stress is a efficient method to select suspension cell line of higher productivity of flavonol glycoside.

Cell Hypoxia↗

Characterization of human and mouse angiopoietin-like factor CDT6 promoters.

PURPOSE: Angiogenesis refers to the latter stage of vascular development. It has been reported that angiopoietin-like factor cornea-derived transcript 6 (CDT6) encodes a protein homologous to angiopoietins that could play a critical role in blocking a receptor of angiopoietin (Tie2) and therefore contribute to the avascularity and transparency of the cornea in the developing embryo and the adult. This study was focused on isolation and characterization of the CDT6 promoter. METHODS: Rapid amplification of cDNA ends (5'-RACE) was used to isolate the CDT6 promoter from an adaptor-ligated genomic DNA fragment library and to identify the transcription initiation site of the CDT6 gene. The RNase protection assay was performed to confirm the initiation site. The sequence similarity, binding sites for putative transcription factors, and transcriptional activity of human and mouse CDT6 promoters were compared. Corneal and noncorneal cells from humans and other animals were transiently transfected with CDT6 promoter-chloramphenicol acetyltransferase (CAT) reporter constructs to analyze the transcriptional activity of the promoter. RESULTS: A 2956-bp human CDT6 promoter fragment and a 3142-bp mouse CDT6 promoter fragment were isolated. The major transcription initiation sites of the human and mouse CDT6 genes were located at 224 and 168 bp, respectively, upstream of the translation initiation site. Human and mouse CDT6 promoter sequences were very similar. Both promoters were minus TATA and CAAT boxes close to the transcription initiation site. Transfection into human corneal and noncorneal cells and into nonhuman cells revealed that the human CDT6 promoter probably contains positive and negative cis-regulatory elements that modulate cell, tissue, and species specificity. The human CDT6 promoter contains four interferon (IFN)-stimulated response elements (ISREs). No ISREs could be identified in the mouse promoter. IFN-alpha stimulated transcriptional activity of the human promoter. CONCLUSIONS: The human and mouse CDT6 promoters have similar sequences and share many cis-regulatory elements. IFN-alpha appears to have an important role in regulating transcription of the human, but not the mouse, CDT6 promoter.

Angiogenesis Inducing Agents↗