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Biomedical subjects

L Zhou

Publications and source records attributed to L Zhou.

At least 19 recordsLinked to original sources
PubMed2007

Porcine kallikrein gene family: genomic structure, mapping, and differential expression analysis.

Kallikreins belong to a family of serine proteases that are widespread throughout living organisms, expressed in diverse tissue-specific patterns, and known to have highly diverse physiological functions. The 15 human and 24 mouse kallikreins have been implicated in pathophysiology of brain, kidney, and respiratory and reproductive systems and often are used as cancer biomarkers. To better elucidate the structure and evolutionary origin of this important gene family in the pig, we have constructed a contiguous BAC clone-derived physical map of the porcine kallikrein gene region and have fully sequenced a BAC clone containing 13 kallikrein genes, 11 of which are novel. Radiation hybrid mapping assigns this kallikrein-gene-rich region to porcine chromosome 6. Phylogenetic and percent identity plot-based analyses revealed strong structure and order conservation of kallikreins among four mammalian species. Reverse transcriptase-polymerase chain reaction-based expression analysis of porcine kallikreins showed a complex expression pattern across different tissues with the thymus being the only tissue expressing all 13 kallikrein genes. [The sequence data described in this paper has been submitted to GenBank under Accession No. AC149292].

Animals↗
PubMed2006

Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134).

BACKGROUND AND PURPOSE: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators. KEY RESULTS: Five analogues, belonging to two different structural series and display higher binding affinities for ERalpha than ERbeta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ERalpha or ERbeta and oestrogen-response element-driven luciferase. The estimated IC(50) value was 0.52 nM for ERalpha and 2.94 nM for ERbeta, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 microM. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable. CONCLUSIONS AND IMPLICATIONS: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use.

Animals↗
PubMed2006

Role of 2-5A-dependent RNase-L in senescence and longevity.

Senescence is a permanent growth arrest that restricts the lifespan of primary cells in culture, and represents an in vitro model for aging. Senescence functions as a tumor suppressor mechanism that can be induced independent of replicative crisis by diverse stress stimuli. RNase-L mediates antiproliferative activities and functions as a tumor suppressor in prostate cancer, therefore, we examined a role for RNase-L in cellular senescence and aging. Ectopic expression of RNase-L induced a senescent morphology, a decrease in DNA synthesis, an increase in senescence-associated beta-galactosidase activity, and accelerated replicative senescence. In contrast, senescence was retarded in RNase-L-null fibroblasts compared with wild-type fibroblasts. Activation of endogenous RNase-L by 2-5A transfection induced distinct senescent and apoptotic responses in parental and Simian virus 40-transformed WI38 fibroblasts, respectively, demonstrating cell type specific differences in the antiproliferative response to RNase-L activation. Replicative senescence is a model for in vivo aging; therefore, genetic disruption of senescence effectors may impact lifespan. RNase-L-/- mice survived 31.7% (P<0.0001) longer than strain-matched RNase-L+/+ mice providing evidence for a physiological role for RNase-L in aging. These findings identify a novel role for RNase-L in senescence that may contribute to its tumor suppressive function and to the enhanced longevity of RNase-L-/- mice.

Aging↗
PubMed2006

Cloning, chromosomal localization and expression patterns of porcine Kruppel-like factors 4, -5, -7 and the early growth response factor 2.

Kruppel-like factors (KLF) and the early growth response factor 2 (EGR2) are important zinc finger transcription factors in vertebrates. We have cloned the full length coding sequence (CDS) of porcine KLF5, KLF7 and EGR2, which are 1374, 909 and 1416 bp, respectively. KLF4, KLF5 and EGR2 were then chromosomally mapped to porcine 1q28-29, 11q13-14 and 14q23-25, respectively. Moreover, the tissue expression patterns of KLF4, KLF5, KLF7 and EGR2 imply their probable roles in specific tissues. This is the first report of the basic study of these zinc finger transcription factors in pigs; this information will be helpful for future functional studies.

Animals↗
PubMed2006

Adsorbate coverages and surface reactivity in methanol oxidation over Cu(110): An in situ photoelectron spectroscopy study.

The adsorbate species present during partial oxidation of methanol on a Cu(110) surface have been investigated in the 10(-5) mbar range with in situ x-ray photoelectron spectroscopy and rate measurements. Two reaction intermediates were identified, methoxy with a C 1s binding energy (BE) of 285.4 eV and formate with a C 1s BE of 287.7 eV. The c(2x2) overlayer formed under reaction conditions is assigned to formate. Two states of adsorbed oxygen were found characterized by O 1s BE's of 529.6 and 528.9 eV, respectively. On the inactive surface present at low T around 300-350 K formate dominates while methoxy is almost absent. Ignition of the reaction correlates with a decreasing formate coverage. A large hysteresis of approximately 200 K occurs in T-cycling experiments whose correlation with adsorbate species was studied with varying oxygen and methanol partial pressures. The two branches of the hysteresis differ mainly in the amount of adsorbed oxygen, the methoxy species, and a carbonaceous species. Methoxy covers only a minor part of the catalytic surface reaching at most 20%. Above 650 K the surface is largely adsorbate-free.

Journal Article↗
PubMed2006

Puerarin injection for unstable angina pectoris.

BACKGROUND: Puerarin is extracted from the Chinese herb puerariae lobata. Many users of Chinese herbal medicine believe that puerarin has positive effects in the treatment of coronary heart disease (CHD). In recent years puerarin injection has been widely used to treat CHD and angina pectoris. OBJECTIVES: To assess the benefits and harms of puerarin injection for unstable angina. SEARCH STRATEGY: The following electronic databases were searched: The Cochrane Controlled Trials Register on The Cochrane Library (Issue 3, 2004), MEDLINE (1995 to 2004), EMBASE (1995 to 2004), CBM (1995 to 2004), Chinese Cochrane Centre Controlled Trials Register (to 2004), Current Controlled Trials (www.controlled-trials.com) and The National Research Register. We also hand searched 60 Chinese traditional medicine journals. SELECTION CRITERIA: Randomised controlled trials undertaken on adults with unstable angina evaluating the following types of interventions: Puerarin injection compared to western drugs or placebo, or puerarin injection used with western drugs compared to western drugs alone. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed independently by two reviewers. Differences in data extraction and analysis were resolved by consensus, referring back to the original article. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: 20 trials involving 1240 people were included. All trials identified were classified as having a high risk of bias because of poor reported methodology. The duration of treatment was 7-20 days and no information supplied suggested longer follow-ups were conducted for any trials. This limited the observation to participants who were not undertaking normal activities of daily living. The primary outcome (death) was not report in any trial. For all the secondary outcome measures, frequency of acute angina attacks, improvements in ECG, doses and incidence of nitroglycerine needed and levels of plasma endothelin, there was no evidence that puerarin had better or worse effects to other conventional treatments. There was strong evidence to suggest that puerarin injection plus western drugs was a better treatment option than western drugs alone. AUTHORS' CONCLUSIONS: Puerarin injection may be effective in unstable angina when used in addition to conventional treatments. However, these finding should be interpreted with care because of the very low methodological quality of studies and potential publication bias. In the light of the findings, a more rigorously designed, randomised double-blind placebo-controlled trial is needed.

Adult↗
PubMed2006

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas.

Ahi-1 (Abelson helper integration site 1) is a novel gene frequently activated by provirus insertional mutagenesis in murine leukemias and lymphomas. Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in human leukemia cells, particularly in cutaneous T-cell lymphoma cell lines where increases in AHI-1 transcripts of 40-fold are seen. To test directly whether deregulated expression of AHI-1 contributes to their transformed properties, knockdown of AHI-1 expression in Hut78 cells, a cell line derived from a patient with Sezary syndrome (SS), was performed using retroviral-mediated RNA interference. Retroviral-mediated suppression specifically inhibited expression of AHI-1 and its isoforms in transduced cells by 80% and also reduced autocrine production of interleukin (IL)-2, IL-4 and tumor necrosis factor-alpha (TNFalpha) by up to 85%. It further significantly reduced their growth factor independence in vitro and the ability to produce tumors in immunodeficient mice. Interestingly, aberrant expression of AHI-1, particularly truncated isoforms, was present in CD4+CD7- Sezary cells from some patients with SS. Elevated expression of IL-2 and TNFalpha was also found in these cells. These findings provide strong evidence of the oncogenic activity of AHI-1 in human leukemogenesis and demonstrate that its deregulation may contribute to the development of SS.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Clinicopathological features, post-surgical survival and prognostic indicators of elderly patients with hepatocellular carcinoma.

AIM: Comprehensive data regarding elderly patients with hepatocellular carcinoma (HCC) were limited. The present study aims to widen the knowledge based on patients in China. METHODS: Fifty-four elderly (> or =65 years) and 125 non-elderly HCC patients undergoing hepatectomy were enrolled in this retrospective study. Clinicopathological features and post-surgical survival were compared between two groups. Prognostic indicators of elderly patients were defined by uni- and multivariate analyses. RESULTS: Contrast to non-elderly patients, the elderly presented significantly lower rates of HBsAg positivity, Child-Pugh grade A, alpha-fetoprotein (AFP) marked elevation, portal vein tumour thrombosis (PVTT), satellite nodule, and intrahepatic recurrence, smaller tumour sizes, earlier TNM staging and better histological differentiation. No significant differences were found in perioperative mortality rate and post-surgical survival between two groups. PVTT and Edmondson-Steiner grading were identified as independent prognostic indicators of both overall and disease-free survival by multivariate analysis, whereas Child-Pugh grading independently affected the overall survival. CONCLUSIONS: HCC in the elderly seemed to be less HBV-associated, less progressive and less aggressive than that in the non-elderly. Hepatectomy for the elderly could make a satisfactory prognosis and be well tolerated. Some tumour-related factors independently predict the prognosis of elderly HCC patients, and their liver function status should be further valued.

Aged↗
PubMed2006

Tripodal bis(imidazole) thioether copper(I) complexes: mimics of the Cu(B) site of hydroxylase enzymes.

Tripodal bis(imidazole) thioether ligands and the corresponding copper(I) complexes [(BIMT-OR)Cu(L)]PF6 [L = CH3CN (2), CO (3); R = H (a), CH3 (b)] have been prepared as models for the Cu(B) site of copper hydroxylase enzymes. The IR (CO) values of 3a and 3b (L = CO) are comparable to those of the carbonylated enzymes. The reaction of 2a with O2 gives dinuclear complex 4 with bridging BIMT-O ligands and oxidized -SMe groups, whereas oxygenation of 2b affords [(BIMT-OMe)2Cu2O(H)2](CF3SO3)2 (5) and Cu(BIMT-OMe)(DMF)2](PF6)2 (6).

Copper↗
PubMed2006

Dose-related antiallodynic effects of cyclic AMP response element-binding protein-antisense oligonucleotide in the spared nerve injury model of neuropathic pain.

A transcription factor known as cyclic AMP response element-binding protein has been shown to be involved in the central sensitization in neuropathic pain and inflammation pain. The present study examined the roles of cyclic AMP response element-binding protein and of the phosphorylated cyclic AMP response element-binding protein in the maintenance of mechanical and cold allodynia induced by a neuropathic pain model, "spared nerve injury," in rats. First, the results of immunohistochemical study showed that phosphorylated cyclic AMP response element-binding protein, but not cyclic AMP response element-binding protein, increased bilaterally in the spinal dorsal horn 14 days following spared nerve injury, indicating a possible contribution of phosphorylated cyclic AMP response element-binding protein in spared nerve injury. Second, chronic intrathecal application of cyclic AMP response element-binding protein antisense oligodeoxynucleotide with three doses (10 microg/day, 20 microg/day and 40 microg/day) for 5 days demonstrated that the higher doses (20 and 40 microg) significantly attenuated both mechanical (bilaterally) and cold (ipsilaterally) allodynia, compared with sense oligodeoxynucleotide and the lower dose (10 microg). Western blot results showed that the alleviation in intensity of behavioral performance was accompanied by a significant reduction of total cyclic AMP response element-binding protein and phosphorylated cyclic AMP response element-binding protein in the spinal dorsal horn. Moreover, there were no differences in cyclic AMP response element-binding protein and phosphorylated cyclic AMP response element-binding protein between ipsilateral and contralateral dorsal horns. Our data demonstrate a close association between the expression of behavioral hypersensitivity and cyclic AMP response element-binding protein activation in the spinal dorsal horn following spared nerve injury, supporting the notion that phosphorylated cyclic AMP response element-binding protein may play an important role in the maintenance of chronic neuropathic pain.

Animals↗
PubMed2006

Type I collagen is a molecular target for inhibition of angiogenesis by endogenous thrombospondin-1.

Three-dimensional explant cultures of muscle tissue were used to characterize secreted proteins regulated by endogenous levels of the angiogenesis modulator thrombospondin (TSP)-1. Explants from TSP1 null mice exhibit enhanced neovascularization associated with increased endothelial outgrowth but decreased outgrowth of perivascular smooth muscle cells . The absence of endogenous TSP1 did not diminish activation of latent transforming growth factor-beta and moderately decreased matrix metalloproteinase levels. However, significant changes in other secreted proteins were observed. Endogenous TSP1 decreased mRNA levels for collagens Ialpha1, Ialpha2, and IIIalpha1 and laminin alpha4 and increased collagen IValpha1 mRNA expression. Endogenous TSP1 also decreased the level of type I collagen protein produced by the vascular outgrowths. Collagens Ialpha1, Ialpha2, and IIIalpha1 are known tumor endothelial markers, suggesting that TSP1 coordinately regulates a set of extracellular matrix genes that reverse the angiogenic switch. Suppression of collagen Ialpha1 or Ialpha2 mRNAs using antisense morpholinos inhibited outgrowth in TSP1 null explants and proliferation of TSP1 null endothelial cells, indicating that type I collagen synthesis is limiting for this neovascularization response.

Angiogenesis Inhibitors↗
PubMed2006

Safety of extended treatment with anakinra in patients with rheumatoid arthritis.

OBJECTIVE: To determine the safety profile of anakinra after extended exposure in a diverse clinical trial population of patients with rheumatoid arthritis. METHODS: A six month, randomised, double blind phase comparing anakinra (100 mg/day) with placebo was followed by open label anakinra treatment for up to three years in patients with rheumatoid arthritis. Concomitant non-steroidal anti-inflammatory drugs, corticosteroids, and other disease modifying antirheumatic drugs were permitted. RESULTS: In all 1346 patients with rheumatoid arthritis received anakinra for up to three years. Patients had varying levels of disease severity, concomitant drug use, and comorbid conditions. Cumulative, exposure adjusted event (EAE) rates for all adverse events (AEs), serious AEs, and deaths were similar during each year of anakinra treatment; the overall rate (0 to 3 years) was similar to that observed for controls during the blinded phase. The most frequent AEs were injection site reactions (122.26 events/100 patient-years), rheumatoid arthritis progression (67.80 events/100 patient-years), and upper respiratory infections (26.09 events/100 patient-years). The EAE rate of serious infections was higher for patients treated with anakinra for 0 to 3 years (5.37 events/100 patient-years) than for controls during the blinded phase (1.65 events/100 patient-years). However, if the patient was not receiving corticosteroid treatment at baseline, the serious infection rate was substantially lower (2.87 event/100 patient-years). The overall incidence of malignancies was consistent with expected rates reported by SEER. Neutralising antibodies developed in 25 patients, but appeared to be transient in 12; neutralising antibody status did not appear related to occurrence of malignancies or serious infections. There were no clinically significant trends in laboratory data related to anakinra. CONCLUSION: Anakinra is safe and well tolerated for up to three years of continuous use in a diverse population of patients with rheumatoid arthritis.

Adult↗
PubMed2006

Prevalence of human cytomegalovirus UL97 D605E mutation in transplant recipients in China.

Human cytomegalovirus (CMV) resistance to gancyclovir (GCV) occurs via mutation in the UL97 gene, ethylene diamine tetraacetic acid blood samples were obtained from 23 transplant recipients who received a GCV implant. A nested polymerase chain reaction amplifying UL97 codons 450 to 672 was performed. Nested amplifications were sequenced directly. No known UL97 GCV resistance mutations were found. Eighteen of 23 patients (78%) had revealed mutations at codon 605 (D to E). Mutant D605E may reverse to wild-type during the follow-up treatment. We conclude that human CMV UL97 D605E mutation occurred in Chinese transplant recipients. This mutation may be regarded as a natural sequence variant.

Bone Marrow Transplantation↗
PubMed2006

Fatty acids inhibit intramyocellular triglyceride synthesis and turnover acutely in high fat-fed obese rats.

Obesity is associated with hyperlipidemia and enlarged intramyocellular triglyceride (imcTG) stores. The latter is strongly correlated with muscle insulin resistance. However, whether hyperlipidemia plays a role in imcTG accumulation is unknown. In the present study, the effects of plasma fatty acids on imcTG fractional turnover rate (FTR) and synthesis in skeletal muscle of high fat-fed obese rats have been examined using pulse-chase technique. imcTG was prelabeled (pulse) by continuous infusion of U- (14)Cglycerol and then the loss of (14)C-labels from imcTG was chased while exogenous fatty acids were infused at 0 (saline), 1 (L) or 3 (H) micromol/kg/min. imcTG synthesis was determined using 2- (3)Hglycerol during the chase. L and H fatty acid infusions raised plasma fatty acids by 14% (p=0.02) and 30% (p=0.001), respectively, while plasma insulin and glycerol and the rate of glycerol appearance remained unchanged (p>0.05). imcTG FTR was suppressed by 36-40% and 48% in gastrocnemius and tibialis anterior, respectively (both p<0.05), and imcTG synthesis was suppressed by 50-60% in the same muscles (both p<0.05). In contrast, neither turnover nor synthesis of imcTG in soleus was affected by fatty acid infusion (p>0.05). imcTG content and the activities of diglyceride acyltransferase and hormone sensitive lipase were not affected by fatty acid infusion. The findings suggested that elevated plasma fatty acids suppress imcTG turnover and synthesis simultaneously and thus do not appear to promote imcTG accumulation in this obesity model at least in short term.

Animals↗
PubMed2006

Synthesis of three natural diosgenyl glycosides.

Three well-known natural diosgenyl glycosides which have the same sugar chains but different sequence, ophipogonin C', polyphillin C and prosapogenin B, were synthesised by a facile approach. A method using the levulinyl group as a protecting group to selectively mask the C3-OH of diosgenyl 4,6-O-benzylidene-beta-D-glucopyranoside is described.

Chromatography, Thin Layer↗
PubMed2006

Increased expression of Toll like receptor 4 on peripheral-blood mononuclear cells in patients with coronary arteriosclerosis disease.

The family of Toll-like receptors (TLRs) initiates innate immune responses, and Toll-like receptor 4 (TLR4) was considered to be an important player in the initiation and progression of atherosclerotic disease. The aim of the study was to investigate the expression of TLR4 on peripheral-blood mononuclear cells (PBMCs) in patients with coronary arteriosclerosis disease (CAD). We have examined the expression of TLR4 protein and mRNA by flow cytometry (FCM) and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). In addition, the levels of plasma lipids were determined by automatic biochemistry analyzer. The results showed that the positive rates and the mean mRNA copy number of TLR4 in CAD group were significantly higher than that in controls. But no significant difference was found in the positive rate and the mean mRNA copy number of TLR4 between CAD group with normal level of plasma lipids and the CAD group with abnormal level of plasma lipids. We suggest that expression level of TLR4 on peripheral-blood mononuclear cells is increased in atherosclerotic, but the differential expression of TLR4 has no correlation with the level of plasma lipids.

Aged↗
PubMed2006

Cloning, chromosome mapping and expression characteristics of porcine ANGPTL3 and -4.

Angiopoietin-like protein 3 and -4 (ANGPTL3 and -4) are two members of angiopoietin-like proteins (ANGPTLs), which have the signature structure of the angiopoietin family but cannot bind to the TIE2 receptor. It has been reported that they both affect lipid metabolism by inhibiting the activity of lipoprotein lipase (LPL). Here we report the cDNA cloning, chromosome mapping and expression analysis of ANGPTL3 and -4 in pigs. Sequence analysis shows that ANGPTL3 contains an open reading frame of 1,389 bp, which encodes 462 amino acids, and ANGPTL4 contains a coding region of 1,239 bp, which encodes 412 amino acids. Porcine ANGPTL3 deduced amino acid sequence shares 83% and 73.7% identity with human and mouse, respectively, and ANGPTL4 shares 79.4% and 77.7% amino acid identity with human and mouse, respectively. Porcine ANGPTL3 and -4 were mapped to the 6q31-->q35 and 2q21-->q24 region, respectively, by radiation hybrid mapping. Tissue distribution analysis indicated that porcine ANGPTL3 mRNA was exclusively expressed in liver, and porcine ANGPTL4 was ubiquitously expressed with the highest abundance in white adipose tissue. Furthermore, the mRNA level of ANGPTL3 and -4 in liver and the mRNA level of ANGPTL4 in white adipose tissue were significantly higher in genetically obese pigs than in their lean counterparts. This is the first report of molecular cloning and characterization of ANGPTL3 and -4 in pigs, which will be helpful for a better understanding of the role of ANGPTLs in lipid metabolism.

3' Untranslated Regions↗