Biomedical subjects

Xin Li

Publications and source records attributed to Xin Li.

At least 91 records · Page 5Linked to original sources

PubMed2006

Karyotype analysis of Gossypium arboreum x G. bickii by genome in situ hybridization.

By using genome in situ hybridization (GISH) on root somatic chromosomes of allotetraploid derived from the cross Gossypium arboreum x G. bickii with genomic DNA (gDNA) of G. bickii as a probe, two sets of chromosomes, consisting of 26 chromosomes each, were easily distinguished from each other by their distinctive hybridization signals. GISH analysis directly proved that the hybrid G. arboreum x G. bickii is an allotetraploid amphiploid. The karyotype formula of the species was 2n = 4x = 52 = 46m (4sat) + 6sm (4sat). We identified four pairs of satellites with two pairs in each sub-genome. FISH analysis using 45S rDNA as a probe showed that the cross G. arboreum x G. bickii contained 14 NORs. At least five pairs of chromosomes in the G sub-genome showed double hybridization (red and blue) in their long arms, which indicates that chromatin introgression from the A sub-genome had occurred.

Chromatin↗

PubMed2006

Zirconium phosphonate-modified porous silicon for highly specific capture of phosphopeptides and MALDI-TOF MS analysis.

Phosphorylation is one of the most important post-translational modifications of proteins, which modulates a wide range of biological functions and activity of proteins. The analysis of phosphopeptides is still one of the most challenging tasks in proteomics research by mass spectrometry. In this study, a novel phosphopeptide enrichment approach based on the strong interaction of zirconium phosphonate (ZrP) modified surface with phosphopeptides has been developed. ZrP modified porous silicon (ZrP-pSi) wafer was prepared to specifically capture the phosphopeptides from complex peptide mixtures, and then the captured phosphopeptides were analyzed by MALDI-TOF MS by directly placing the wafer on a MALDI target. The phosphopeptide enrichment and MALDI analysis were both performed on the ZrP-pSi wafer which significantly reduced the sample loss and simplified the analytical procedures. The prepared ZrP-pSi wafer has been successfully applied for the enrichment of phosphopeptides from the tryptic digest of standard phosphoproteins beta-casein and alpha-casein. The excellent selectivity of this approach was demonstrated by analyzing phosphopeptides in the digest mixture of beta-casein and bovine serum albumin with molar ratio of 1:100. High detection sensitivity has been achieved for the analysis of the phosphopeptides from tryptic digestion of 2 fmol beta-casein on the ZrP-pSi surface.

Amino Acid Sequence↗

PubMed2006

Wrinkled petals and stamens 1, is required for the morphogenesis of petals and stamens in Lotus japonicus.

Although much progress has been made in understanding how floral organ identity is determined during the floral development, less is known about how floral organ is elaborated in the late floral developmental stages. Here we describe a novel floral mutant, wrinkled petals and stamens1 (wps1), which shows defects in the development of petals and stamens. Genetic analysis indicates that wps1 mutant is corresponding to a single recessive locus at the long arm of chromosome 3. The early development of floral organs in wps1 mutant is similar to that in wild type, and the malfunction of the mutant commences in late developmental stages, displaying a defect on the appearance of petals and stamens. In the mature flower, petals and stamen filaments in the mutant are wrinkled or folded, and the cellular morphology under L1 layer of petals and stamen filaments is abnormal. It is found that the expression patterns of floral organ identity genes are not affected in wps1 mutants compared with that of wild type, consistent with the unaltered development of all floral organs. Furthermore, the identities of epidermal cells in different type of petals are maintained. The histological analysis shows that in wps1 flowers all petals are irregularly folded, and there are knotted structures in the petals, while the shape and arrangement of inner cells are malformed and unorganized. Based on these results, we propose that Wps1 acts downstream to the class B floral organ identity genes, and functions to modulate the cellular differentiation during the late flower developmental stages.

Flowers↗

PubMed2006

Clonal persistence and evolution during a decade of recurrent melanoma.

A patient with metastatic cutaneous melanoma responsive to immunotherapy experienced several recurrences over a decade of observation. With each recurrence, biopsies were obtained and cell lines generated. A rare mutation of the beta-catenin gene and an unbalanced methylation of the androgen receptor were documented in all cell lines. Karyotyping and comparative genomic hybridization identified consistent genetic traits in spite of divergent phenotypes, suggesting that all the metastases were derived from the same primary tumor, although they were each probably not derived from the most recent previous metastasis in a sequential manner. Thus, metastatic melanoma recurs from a common progenitor cell and phenotypic changes occur around a central core of genetic stability. This observation may bear significance for the development of targeted anticancer therapies.

Cell Line, Tumor↗

PubMed2006

Quantification of small molecule-receptor affinities and kinetics by acoustic profiling.

The label-free RAPid 4 system that exploits resonant acoustic profiling (RAP) from Akubio (Cambridge, UK) was used to determine the affinity and kinetics for several different small molecule-receptor interactions. This was achieved by attaching the target receptor to the surface of quartz crystal resonators through a variety of specific coupling chemistries, followed by application of a small-molecular-weight ligand to the receptor via a microfluidic flow-based delivery system. Rank order of binding was determined for very weak interactions such as cofactor binding to glucose dehydrogenase. Moderate interaction affinities and binding kinetics could be determined for biotin binding to a specific antibody, and also for several low-molecular-weight sulfonamide analogues binding to human carbonic anhydrase isoform II. The equilibrium binding constants were in general agreement with the values obtained by kinetic analysis of the data, as well as with previously published values obtained using surface plasmon resonance, stopped flow fluorescence, and isothermal titration calorimetry.

Acoustics↗

PubMed2006

A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats.

Aberrations in methylation profile of the genome occur in human cancers induced by folate deficiency. To elucidate the underlying mechanism, male F344 rats were fed a diet deficient in l-methionine and devoid of folic acid and choline (FMD diet), which is known to induce hepatocellular carcinomas. We investigated changes in the DNA methylation machinery, namely, de novo DNA methyltransferases (Dnmt3a and 3b), maintenance DNA methyltransferase (Dnmt1), and methyl CpG binding proteins (MBDs), in rat livers during early stages of tumorigenesis. RT-PCR and Western blot analyses revealed differential expression of these proteins in the livers of rats fed the FMD diet. Although the hepatic Dnmt1 mRNA level declined with age (P < 0.001), it was elevated (P < 0.001) in deficient rats compared with controls. The changes in hepatic Dnmt1 protein level with the diet correlated with its mRNA levels (r = 0.60, P = 0.002). Similarly, the Dnmt3a mRNA level was elevated in rats fed the FMD diet (P < 0.001), whereas the Dnmt3b level (mRNA and protein) was not affected by diet or age. Compared with controls, hepatic MBD1-3 RNA levels increased (P < 0.001) and the protein levels of MBD1, 2, and 4 were elevated (P < 0.001) in the deficient rats. In both diet groups, hepatic MBD2 protein decreased (P < 0.001), whereas MeCP2 protein increased (P < 0.001) with age. These results demonstrate that a combined folate and methyl deficiency alters components of the DNA methylation machinery by both transcriptional and posttranscriptional mechanisms during early stages of hepatocarcinogenesis.

Animals↗

PubMed2006

The indirect costs of arthritis resulting from unemployment, reduced performance, and occupational changes while at work.

OBJECTIVE: The objective of this study was to assess the cost attributable to lost productivity from arthritis and the association between the degree of loss and demographic, disease-related, occupational, and psychosocial variables for people. METHODS: In a prospective study, 383 employed individuals with arthritis were recruited from southwestern Ontario, Canada. Respondents completed structured questionnaires assessing demographic, disease-related, workplace, and psychosocial variables as well as employment-related transitions at 2 time points 18 months apart. Indirect costs resulting from arthritis-related absences, reduced performance, decreased work hours, job change, and work disability were estimated. A proportional odds model was used to assess the impact of the various variables on lost productivity. RESULTS: The average cost attributable to arthritis was CAN Dollars 11,553(Dollars CAN = 0.75 Dollars US) per person per year. The largest component of the loss was the result of reduced performance at work, which accounted for 41% (Dollars 4724) of the total loss. This was followed by wage loss resulting from stopping working or changing jobs, which comprised 37% (Dollars 4309) of the total. Another 12% (Dollars 1398) and 10% (Dollars 1121) of the loss were the result of the decrease in hours of work and absenteeism, respectively. Four variables were associated with the productivity loss: greater symptom severity (odds ratio [OR] = 1.11), low or medium control over the work schedule (OR = 0.55 and 0.60, respectively), greater workspace limitation (OR = 1.10), and higher depression (OR = 1.04). CONCLUSIONS: Indirect arthritis-related costs are substantial. Our results show that not only the disease itself, but also psychosocial and work-related factors affect the magnitude of the costs.

Absenteeism↗

PubMed2006

Endoscopic treatment for atypical manifestations of gastroesophageal reflux disease.

OBJECTIVES: Atypical manifestations are common in patients with gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the response of atypical manifestations of GERD to endoscopic antireflux treatment. METHODS: Patients with atypical manifestations of GERD including hoarseness, cough, wheezing, and non-cardiac chest pain were studied. Endoscopic antireflux treatment consisted of placement of sutures below the squamo-columnar junction. Clinical response was defined as complete resolution of the atypical symptom. Patients were followed clinically for up to 3 yr after the procedure. Short-term response was evaluated within 6 months of the procedure, and long-term follow-up was determined 1-3 yr after the procedure. RESULTS: Forty-three patients met the inclusion criteria; four patients underwent repeat procedures during the study period and were excluded from the analysis. Long-term follow-up was available in all 39 patients. Short-term response counts were: hoarseness, 12 of 19 patients, cough, 17 of 19; wheezing, 8 of 9; and chest pain, 13 of 18. Long-term follow-up of patients (mean of 18 months) for these symptoms was not significantly different compared to short-term response. CONCLUSIONS: Endoscopic suturing of the gastroesophageal junction appears to be a possible treatment option for atypical manifestations of GERD and future studies are needed to determine its role in management.

Adult↗

PubMed2006

Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia.

AIM: To study the multiple dose clinical pharmacokinetics of risperidone and its main active metabolite, 9-hydroxyrisperidone, in Chinese female patients with schizophrenia. METHODS: The subjects were 23 Chinese female inpatients aged 18-65 years who met the CCMD-III (third revision of the Chinese Criteria of Mental Disorders) criteria for schizophrenia. Subjects were tested after 17 d of treatment with 2 mg risperidone twice daily. Plasma concentrations of risperidone and 9-hydroxy-risperidone were assayed by using validated high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. RESULTS: Risperidone was rapidly absorbed (Tmax was 1.6 h) and its T1/2 in plasma was short (3.2 h). 9-hydroxy-risperidone was quickly metabolized from the parent drug with a mean Tmax of 2.5 h. It had a long half-life of 24.7 h. The C(ss)(av) of risperidone and 9-hydroxy-risperidone were 36.9+/-33.1 and 110.6+/-30.5 microg x h x L(-1), respectively, and the AUC(ss)0-12 were 443.2+/- 397.4 and 1327.2+/- 402.3 microg x h x L(-1), respectively. CL/F and V/F of risperidone were 8.7+/- 6.2 L/h and 34.1+/- 24.3 L, respectively. Interindividual variations for pharmacokinetic parameters were quite large for risperidone. All 23 subjects experienced high prolactin levels when treated with risperidone. However there was no correlation between prolactin level and the concentration of risperidone, 9-hydroxy-risperidone, or the active moiety. CONCLUSION: Risperidone showed large interindividual variations in pharmacokinetics. Administration of risperidone resulted in high serum prolactin levels. The results indicate that systemic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizophrenic patients is higher relative to published data for white Caucasian patients. Larger studies regarding the PK/PD relationship may be required to develop a reasonable clinical dosage regimen for Chinese female patients.

Adolescent↗

PubMed2006

Construction of a small peptide library related to inhibitor OM99-2 and its structure-activity relationship to beta-secretase.

AIM: To develop probes for detecting the binding specificity between beta-secretase and substrate, and provide reliable biological activity data for further researching encircling substrate-based inhibitors. METHODS: To prepare the inhibitors, the hydroxyethylene (HE) segment including P1 and P1'was synthesized after multi-step reactions; the combination of all segments was then completed through solid phase synthesis. Recombinant human beta-secretase ectodomain (amino acid residues 1-460) was expressed as a secreted protein with a C-terminal His tag in insect cells using baculovirus infection, and all compounds were evaluated in this beta-secretase enzyme assay. In order to understand the interaction in detail, the theoretical methods, namely molecular dynamics (MD) simulation and molecular mechanics-generalized-born surface area (MM-GBSA) analysis, were performed on the complex of beta-secretase and OM99-2 to obtain the geometrical and energetical information. RESULTS: We designed and constructed a positional scanning combinatorial library including 16 compounds; all members of the library were synthesized based on HE dipeptide isostere. Structure-activity relationship studies at the P4-P1 and P1' -P4'positions led to the discoveries of P and P'sides binding specificity and potent inhibitors 14, 18, and 22. The binding free energy on the whole system and every residue were compared to the biological assay result. CONCLUSION: The removal of P4' yielded inhibitor 22 (A3 *B2) with high potency; further truncation of P3'gave inhibitor 18 (A3 *B1) with equal activity, implying that the right side of the inhibitors play a less important role and could be easily simplified, while change on the P side may cause substantial results.

Amyloid Precursor Protein Secretases↗

PubMed2006

Borrelia burgdorferi lacking BBK32, a fibronectin-binding protein, retains full pathogenicity.

BBK32, a fibronectin-binding protein of Borrelia burgdorferi, is one of many surface lipoproteins that are differentially expressed by the Lyme disease spirochete at various stages of its life cycle. The level of BBK32 expression in B. burgdorferi is highest during infection of the mammalian host and lowest in flat ticks. This temporal expression profile, along with its fibronectin-binding activity, strongly suggests that BBK32 may play an important role in Lyme pathogenesis in the host. To test this hypothesis, we constructed an isogenic BBK32 deletion mutant from wild-type B. burgdorferi B31 by replacing the BBK32 gene with a kanamycin resistance cassette through homologous recombination. We examined both the wild-type strain and the BBK32 deletion mutant extensively in the experimental mouse-tick model of the Borrelia life cycle. Our data indicated that B. burgdorferi lacking BBK32 retained full pathogenicity in mice, regardless of whether mice were infected artificially by syringe inoculation or naturally by tick bite. The loss of BBK32 expression in the mutant had no adverse effect on spirochete acquisition (mouse-to-tick) and transmission (tick-to-mouse) processes. These results suggest that additional B. burgdorferi proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle.

Adhesins, Bacterial↗

PubMed2006

The P2X7 receptor: a novel biomarker of uterine epithelial cancers.

OBJECTIVE: To determine expression of the P2X(7) receptor in normal and in cancer uterine tissues. The rationale was that the receptor P2X(7) regulates constitutive apoptosis in uterine epithelial cells, and previous studies showed diminished P2X(7)-mediated apoptosis in cancer uterine cells compared with normal cells. METHODS: A clinical, experimental feasibility study. Normal (n = 42) and cancer uterine tissues (n = 47) were obtained from a total of 72 women ages 25 to 75. End points for P2X(7) mRNA were quantitative PCR and in situ hybridization, and end points for P2X(7) protein were Western blots and immunostaining using anti-P2X(7) antibody. RESULTS: (a) In normal uteri, P2X(7) mRNA and protein were expressed predominantly in the epithelial (endometrial, endocervical, and ectocervical) cells. (b) Expression of the P2X(7) mRNA and protein was absent from endometrial and endocervical adenocarcinoma tissues and from cervical squamous cell carcinoma tissues. (c) In cervical dysplasia, P2X(7) protein was absent in the dysplastic lesions. (d) Semiquantitative analysis using P2X(7) mRNA (normalized in each tissue to the constitutive glyceraldehyde-3-phosphate dehydrogenase) and P2X(7) protein levels (normalized in each tissue to the constitutive tubulin) revealed that P2X(7) mRNA and/or protein levels can distinguish uterine normal from cancer tissues at high degrees of sensitivity (92%, 100%) and specificity (100%, 90%). SUMMARY AND CONCLUSIONS: (a) Levels of the P2X(7) are lower in uterine epithelial cancer tissues than in the corresponding normal tissues. (b) The data suggest that tissue P2X(7) mRNA and protein levels could be used as a novel biomarker to differentiate normal and cancer uterine epithelial tissues.

Adenocarcinoma↗

PubMed2006

Understanding parathyroid hormone action.

In addition to regulating serum calcium and stimulating bone resorption, parathyroid hormone (PTH) is known to stimulate bone formation under certain conditions. The mechanisms behind this counterintuitive anabolic action are largely unknown. We have set out to identify PTH-regulated genes that might be responsible for each of these contrasting effects of the hormone. This article describes our work on a select number of those genes.

Amphiregulin↗

PubMed2006

Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion.

Epidermal growth factor receptor (EGFR) is suggested to be one of the positive factors in the invasive progression of bladder cancer. Id-1 (inhibitor of differentiation or DNA binding), a helix-loop-helix (HLH) transcription factor, was recently identified as a key factor in the EGFR signalling pathway. The aim of this study was to investigate the role of Id-1 in bladder cancer progression and its relation-ship with EGFR. Using clinical specimens from different stages of bladder cancer, immunohistochemical staining was performed to determine if Id-1 expression was positively associated with tumour staging and EGFR expression. The direct role of Id-1 in cancer cell invasion was also investigated through ectopically expressing the Id-1 gene in a RT112 bladder cancer cell line by wound closure and collagen invasion assays. To explore the therapeutic potential of targeting the Id-1 gene in the treatment of invasive bladder cancer, we studied if inactivation of the Id-1 gene through small RNA interference could lead to the suppression of invasion in a MGHU1 bladder cancer cell line. Our results showed that the up-regulation of Id-1 was associated with increased EGFR expression, clinical staging and the invasion ability of bladder cancer cells. Inactivation of Id-1 may be a potential therapeutic target to inhibit the invasion by bladder cancer cells.

Blotting, Western↗

PubMed2006

[Effects of stromal cell-derived factor 1 and platelet factor 4 on the adhesion characteristics and chemotactic function of ex vivo expanded umbilical cord blood CD34+ cells].

To investigate the effects of stromal cell-derived factor 1 (SDF-1) and platelet factor 4 (PF4) on the homing-related function of expanded ex vivo umbilical cord blood CD34(+) cells, purified cord blood CD34(+) cells were cultured in serum-free medium containing a HGF combination of FL + SCF + TPO (FST) with either 100 ng/ml SDF-1 alone, 100 ng/ml PF4 alone, or both of these 2 cytokines. The expansion rate of CD34(+) cells, colony formation, homing-related functions including expression of homing-related adhesion molecules of expanded CD34(+) cell, adhesion activity and chemotactic function of the re-selected expanded CD34(+) cells were evaluated at different time points. The results showed that expansion rate of CD34(+) cells and expansion multiple of CFU in SDF-1 groups were higher than those in control. The expression of CD49e on the expanded CD34(+) cells was remarkable up-regulated, in contrast, expression of CXCR-4 on the expanded CD34(+) cells was remarkable down-regulated in SDF-1 groups. The expression of CD49e, CD54 and CXCR-4 on the expanded CD34(+) cells were remarkably up-regulated in the PF4 groups. In all the SDF-1 group, PF4 group and SDF-1 plus PF4 group, the ability of expanded CD34(+) cells adhering to fibronectin layer were higher than those in the control on day 10. Spontaneous migration rate of expanded CD34(+) cells in SDF-1 groups were higher than those in control, while SDF-1-induced migration rate were lower than those in control on day 10. SDF-1-induced migration rate in PF4 groups were higher than those in control on day 10. Spontaneous and SDF-1-induced migration rate of expanded CD34(+) cells in the SDF-1 plus PF4 groups were higher than those in control on day 10. It is concluded that, SDF-1 and PF4 can up-regulate expression of adhesion molecules on expanded CD34(+) cells, and retain the adherent and migration ability of expanded CD34(+) cells, which is helpful for the homing of expanded CD34(+) cells. In short, SDF-1 and PF4 are helpful for the homing-related function of the expanded UCB HSPC.

Antigens, CD34↗

PubMed2006

[Clinical application of alpha1 adrenoceptor antagonist Naftopidil to the treatment of chronic non-bacterial prostatitis].

OBJECTIVE: To study the efficacy and safety of alpha1 adrenoceptor antagonist Naftopidil in the treatment of chronic non-bacterial prostatitis. METHODS: An opened, self-controlled, multicentral clinical trial was conducted. One hundred and six cases of patients who had been diagnosed as chronic non-bacterial prostatitis (NBP) were treated with Naftopidil (25 mg once a day) for 4 weeks. The efficacy was evaluated by the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and the WBC in the examination of prostatic secretion (EPS) after the treatment. RESULTS: After 4 weeks therapy, 105 cases were evaluable. After treatment, NIH-CPSI total score were averagely decreased 12.0 points (P <0.001), symptom score 7.9 points (P <0.001) and QOL score 4.1 points (P <0.001). There was a statistically significant difference in WBC count ([(15.2 +/- 15.1)/HP vs (9.5 +/- 12.0)/HP, P < 0.01] and max flow rate(MFR) [(19.2 +/- 4.8) ml/s vs (22.7 +/- 4.9) ml/s, P < 0.01]. The total effective rate were 84.8% in the whole group. The clinical adverse rate was 3.81%, including 3 cases of mild dizziness and 1 case of mild inappetence. CONCLUSION: alpha1 adrenoceptor antagonist Naftopidil is effective and safe for the treatment of chronic non-bacterial prostatitis.

Adolescent↗

PubMed2006

[Moxibustion and its application in anti-aging study].

The research on anti-aging technology is always a foreland in the field of researches into human health. Based on a review of the researches for anti-aging, this paper described all kinds of theory of aging and laid the emphasis on the status quo of researches on the use of Traditional Chinese Medicine(TCM) moxibustion for anti-aging, including the research on the theory of the moxibustion in anti-aging, the research on selecting acupoints of moxibustion for anti-aging, and the clinical application of moxibustion in anti-aging in detail. The significance of herbalist theory in anti-aging and the wider development foreground were high-lighted.

Acupuncture Points↗

PubMed2006

[RAPD analysis of Scutellaria baicalensis from different germplasms].

OBJECTIVE: To provide reference for breeding Scutellaria baicalensis from different germplasms,and to explore their genetic diversities and different strains. METHOD: The RAPD method was applied to the study on S. baicalensis from different germplasms by use of 14 random primers about 10 bp, and SAPD-analysis of 34 S. baicalensis from different germplasms was carried out by using the method of withingroups-linkage in SPSS 10.0. RESULTS: 14 among 115 primers were selected to amplify about 165 segments of DNA. Among them, 132 segments of DNA, 80.0% of the total, can represent genetic of diversities of S. baicalensis. According to RAPD analysis, 34 germplasms of S. baicalensis were classified into A, B, C and D categories. CONCLUSION: S. baicalensis from different germplasms shows abundant genetic diversities. Germplasms from Shandong like Mengyin 3, Menyin 2 and Pingyi have close distance (0.315) in genetic background, which can be chosen for breeding of cultivated. Though genetic characters are similar in the morphology, the geological distribution of S. baicalensis and its morphology have not certain correlation. The complex genetic background of S. baicalensis indicate that the work of the selective breeding and management for breeding of S. baicalensis have to be strengthened.

Breeding↗