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Biomedical subjects

Hui Yang

Publications and source records attributed to Hui Yang.

At least 37 records · Page 2Linked to original sources

1,2,4-Oxadiazolidin-3,5-diones and 1,3,5-triazin-2,4,6-triones as cytosolic phospholipase A2alpha inhibitors.

1,2,4-Oxadiazolidin-3,5-dione and 1,3,5-triazin-2,4,6-trione scaffolds were employed as templates to incorporate the pharmacophore requirements of cytosolic phospholipase A2alpha substrate mimetics. Inhibitors that are active in both enzyme, and cell-based assays were identified from both classes. From the SAR work carried out and modeling efforts around these templates, the triazinetrione scaffold with an additional substitution point was found to be more favorable.

Enzyme Inhibitors↗

Adipokine resistin promotes in vitro angiogenesis of human endothelial cells.

OBJECTIVE: Resistin may be associated with obesity and cardiovascular diseases. However, it is unknown whether resistin directly contributes to angiogenesis. In the present study, we evaluated the effects of resistin on angiogenic potential, including endothelial cell proliferation, migration, and capillary-like tube formation. METHODS: Human coronary artery endothelial cells (HCAECs) were treated with resistin. Cell proliferation was evaluated by [3H]thymidine incorporation and MTS assays. Cell migration was assessed by a modified Boyden chamber assay. Capillary-like tube formation was studied with a Matrigel model. Several gene expression levels were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) was determined by Bio-Plex luminex analyzer. Basic fibroblast growth factor (bFGF) was used as a control. Human umbilical vein endothelial cells (HUVECs) and human lung microvascular endothelial cells (HMVEC-L) were also included. RESULTS: Resistin induced both endothelial proliferation and migration in a dose- and time-dependent manner with the maximal effect at 40 ng/ml. Both resistin-induced cell proliferation and migration could be effectively blocked by a resistin-neutralization antibody. In addition, resistin promoted capillary-like tube formation of HCAECs on Matrigel. Resistin also significantly upregulated the mRNA expression of vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2) and matrix metalloproteinases (MMP-1 and MMP-2) at both mRNA and protein levels. Furthermore, transient phosphorylation of ERK1/2 and p38 was observed after the addition of resistin to HCAECs. The resistin-induced cell proliferation and migration were both completely blocked by specific ERK1/2 and p38 inhibitors. CONCLUSIONS: Resistin induces human endothelial cell proliferation and migration, promotes capillary-like tube formation, upregulates the expression of VEGFRs and MMPs, and activates ERK1/2 and p38 pathways. Thus, resistin may play an important role in angiogenesis-associated vascular disorders.

Antibodies, Monoclonal↗

Thymosin beta10 inhibits cell migration and capillary-like tube formation of human coronary artery endothelial cells.

Thymosin beta10 is a cytoplasm G-actin sequestering protein whose functions are largely unknown. To determine the direct effects of exogenous thymosin beta10 on angiogenic potentials as endothelial cell migration and capillary-like tube formation, human coronary artery endothelial cells (HCAECs) were incubated with increasing doses of thymosin beta10 (25-100 ng/ml). By using a modified Boyden chamber assay, thymosin beta10 inhibited cell migration in a dose- and time-dependent manner with the maximal effect being a 36% reduction at 100 ng/ml as compared to controls (P < 0.01). In addition, thymosin beta10 (100 ng/ml) significantly inhibited the capillary-like tube-formation of HCAECs on Matrigel, showing a 21% reduction of the total tube length as compared to negative controls (P < 0.01). Furthermore, by using real time PCR analysis, thymosin beta10 significantly decreased mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1) and integrin alphaV after 24 h treatment in HCAECs. By contrast, thymosin beta4 significantly increased HCAEC migration. These results indicate that thymosin beta10, but not thymosin beta4, have direct inhibitive effects on endothelial migration and tube formation that might be mediated via downregulation of VEGF, VEGFR-1 and integrin alphaV in HCAECs. This study suggests a potential therapeutic application of thymosin beta10 to the diseases with excessive angiogenesis such as cancer.

Capillaries↗

Polyphenolic constituents of Actaea racemosa.

A new lignan, actaealactone (1), and a new phenylpropanoid ester derivative, cimicifugic acid G (2), together with 15 known polyphenols, protocatechuic acid, protocatechualdehyde, p-coumaric acid, caffeic acid, methyl caffeate, ferulic acid, ferulate-1-methyl ester, isoferulic acid, 1-isoferuloyl-beta-d-glucopyranoside, fukinolic acid, and cimicifugic acids A, B, and D-F, were isolated from an extract of the rhizomes and roots of black cohosh (Actaea racemosa). The structures of the new compounds were determined on the basis of NMR spectroscopic analysis. Compounds 1 and 2 displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay with IC(50) values of 26 and 37 microM, respectively. Other antioxidants identified from A. racemosa include cimicifugic acid A (3), cimicifugic acid B (4), and fukinolic acid (5). Compounds 1 and 2 also exhibited a small stimulating effect on the growth of MCF-7 breast cancer cell proliferation 1.24-fold (14 microM) and 1.14-fold (10 microM), respectively, compared to untreated cells.

Biphenyl Compounds↗

Bioactive depsides and anthocyanins from jaboticaba (Myrciaria cauliflora).

A new depside, jaboticabin (1), together with 17 known compounds were isolated from the fruit of jaboticaba (Myrciaria cauliflora). The structure of 1 was elucidated by spectroscopic data interpretation. Known compounds were identified by comparison of their spectroscopic data with literature values or by comparison to authentic standards. Compound 1 and the related depside 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid (2) significantly inhibited chemokine interleukin (IL)-8 production before and after cigarette smoke treatment of cells. Compound 1 was cytotoxic in the HT29 colon cancer cell line (IC50 = 65 microM), and 2 was active against HCT116 colon cancer cells (IC50 = 30 microM). Compounds 1 and 2 also exhibited antiradical activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC50 = 51.4 and 61.8 microM, respectively). Two anthocyanins, cyanidin 3-glucoside (3) and delphinidin 3-glucoside (4), also showed good activity in these assays.

Anthocyanins↗

Functional genomics of genes with small open reading frames (sORFs) in S. cerevisiae.

Genes with small open reading frames (sORFs; <100 amino acids) represent an untapped source of important biology. sORFs largely escaped analysis because they were difficult to predict computationally and less likely to be targeted by genetic screens. Thus, the substantial number of sORFs and their potential importance have only recently become clear. To investigate sORF function, we undertook the first functional studies of sORFs in any system, using the model eukaryote Saccharomyces cerevisiae. Based on independent experimental approaches and computational analyses, evidence exists for 299 sORFs in the S. cerevisiae genome, representing approximately 5% of the annotated ORFs. We determined that a similar percentage of sORFs are annotated in other eukaryotes, including humans, and 184 of the S. cerevisiae sORFs exhibit similarity with ORFs in other organisms. To investigate sORF function, we constructed a collection of gene-deletion mutants of 140 newly identified sORFs, each of which contains a strain-specific "molecular barcode," bringing the total number of sORF deletion strains to 247. Phenotypic analyses of the new gene-deletion strains identified 22 sORFs required for haploid growth, growth at high temperature, growth in the presence of a nonfermentable carbon source, or growth in the presence of DNA damage and replication-arrest agents. We provide a collection of sORF deletion strains that can be integrated into the existing deletion collection as a resource for the yeast community for elucidating gene function. Moreover, our analyses of the S. cerevisiae sORFs establish that sORFs are conserved across eukaryotes and have important biological functions.

Conserved Sequence↗

Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells.

The objective of this study was to determine whether cyclic strain could promote human umbilical vein endothelial cells (HUVECs) to express markers in common with the mature smooth muscle cell (SMC) phenotype, suggesting endothelial cell to SMC transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch and 60 cycles/min for 24-96 hr, and demonstrated elongation with enhanced and organized F-actin distribution. By using real-time polymerase chain reaction analysis, the mRNA levels of five specific SMC markers, SM22-alpha, alpha-smooth muscle actin (alpha-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC), and calponin-1 were significantly increased in cyclic strain-treated HUVECs as compared with those in static control cells. Protein levels of SM22-alpha and alpha-SMA were also substantially increased by Western blot and immunofluorescence staining. In addition, two specific endothelial markers, von Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR-2), showed a reduction in mRNA expression. In addition, cyclic strain-induced increase of SM22-alpha and alpha-SMA expression were reversible when cells were cultured back to the static condition. These results demonstrate a possible endothelial cell to SMC transdifferentiation in response to cyclic strain. Hemodynamic forces in modulating endothelial phenotype may play an important role in the vascular system.

Actins↗

Chromosome or chromatin condensation leads to meiosis or apoptosis in stationary yeast (Saccharomyces cerevisiae) cells.

When starved of essential nutrients, yeast cells cease mitotic division and enter an alternative state called the 'stationary phase'. In this paper, we report that stationary cells enter two major pathways: meiosis and apoptosis. Using transmission electron microscopy, five types of cell were identified in the stationary phase: (1) cells with chromosome condensed nuclei; (2) cells with normal, homogeneously stained nuclei; (3) sporulated cells; (4) apoptotic cells, in which chromatin, but not individual chromosomes, was condensed; and (5) dead cells, in which nuclei and cytoplasm were degraded. Further evidence using live cell imaging and mutation analysis suggested that cells with condensed chromosomes underwent meiosis, whereas chromatin condensed cells underwent apoptotic cell death. Cells with homogeneous nuclei are believed to be in the true resting state and undergo cell death when starvation continues. Chromosome or chromatin condensation may serve as a hallmark of life or death for stationary cells.

Apoptosis↗

EST-based identification of genes expressed in brain and spinal cord of Gekko japonicus, a species demonstrating intrinsic capacity of spinal cord regeneration.

In the present study, a brain and spinal cord cDNA library of Gekko japonicus was constructed, and 2349 unique expressed sequence tags (ESTs), composed of 494 clusters and 1855 singletons, were determined from 4108 randomly selected clones. Of these sequences, 54.8% (1287/2349) ESTs are identified as known genes and 45.2% (1062/2349), as unknown genes. The identified ESTs were classified with respect to their functional categorization; both the housekeeping genes and the nervous system-related genes were well represented in the library. The complete open reading frame (ORF)-containing clones derived from the library were identified as well; 303 clones were obtained to date. Finally, two clones with sequence homology to endothelial differentiation-related factor 1 (EDF-1) and to myelin-associated glycoprotein (MAG) precursor were selected, and their expression patterns in normal and regenerating spinal cord were analyzed by RT-PCR. Both of them were expressed in the spinal cord, and the expression level decreased significantly after tail amputation. This study provides a preliminary view of the gene expression profiles of the central nervous system in gecko, and it might accelerate the process of gene discovery and function analysis in this organism, which demonstrates an intrinsic capacity of spinal cord regeneration.

Animals↗

[Bone marrow necrosis as an initial manifestation of Philadelphia chromosome and myeloid antigens positive B acute lymphoblastic leukemia--a case report].

Many diseases cause bone marrow necrosis (BMN), especially lymphocytic leukemia. To explore the complexity of the pathogenesis and pathology of BMN and understand the multiplicity of clinical features, a case of Philadelphia chromosome positive (Ph+) B acute lymphoblastic leukemia (ALL) expressing myeloid antigens was reported. The results indicated that the clinical features of this case were complicated and multiplex, the diagnosis was confirmed by using bone marrow smear and biopsy, immunophenotype analysis, conventional cytogenetics and fluorescence in situ hybridization (FISH), the prognosis of patients improved by active treatment for primary disease. In conclusion, the Ph+ B ALL expressing myeloid antigen with BMN is very rare, its diagnosis should be confirmed by using multiple methods, and the active treatments should be performed.

Adult↗

[Plasma orexin-A level in patients with obstructive apnea-hypopnea syndrome].

OBJECTIVE: To investigate the effect of uvulopalatopharyngoplasty (UPPP) on changes of plasma orexin-A levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: Fifty-four cases with OSAHS diagnosed by polysomnography were treated with uvulopalatopharyngoplasty and hyoid suspension. Plasma orexin-A levels in patients with OSAHS before and after surgical procedure 6 months, and in 20 healthy people with age,sex and BMI matched controls were measured by radioimmunoassay. The plasma was deproteinized by chromatography. Correlations between orexin-A levels and AHI, MAI and SaO2 min were analyzed. RESULT: The plasma orexin-A levels in the OSAHS group was significantly higher than those in the control group (P < 0.01). Plasma orexin A levels in the patients with OSAHS correlated positively with the AHI (r < 0.658, P < 0.05) and MAI. (r = 0.464, P < 0.05) but correlated negatively with the SaO2 min. The plasma orexin-A levels of 54 responders after 6 months were significantly decreased (P < 0.01) than that of pre-operation, and there is no correlation between plasma orexin-A levels and BMI. CONCLUSION: The plasma orexin-A levels in the OSAHS patients are increased which may be caused by repeated nocturnal apnoea and hypoxia due to OSAHS. Surgical procedures may decreased the plasma orexin-A levels.

Adult↗

[Immunophenotypic and cytogenetic features of acute myelomonocytic leukemia].

BACKGROUND & OBJECTIVE: The expression of some antigens has been involved in cytogenetic abnormalities in leukemia. This study was to explore the immunophenotypes of acute myelomonocytic leukemia (M4), analyze the correlation of M4 to cytogenetic abnormalities, and provide evidences for the diagnosis and therapy. METHODS: Immunophenotypic analysis was performed using a panel of monoclonal antibodies and three-color immunofluorescent staining methods of flow cytometry in 81 patients with M4 leukemia. Cytogenetic records of 73 patients were available, among which 35 were further investigated by dual-color interphase fluorescent in situ hybridization (FISH) and the immunophenotype of inv(16)-positive patients were analyzed. RESULTS: Among the 81 M4 leukemia patients, CD33 (84.0%) was the most commonly expressed antigen, followed by CD13 (81.5%) and CD14 (24.7%). CD34 was detected in 48 (59.3%) patients. T lymphoid-and B lymphoid-associated antigens were expressed in 23 (28.4%) and 10 (12.3%) patients, respectively. All the 11 patients with M4Eo had CD13 expression. CD33, CD34, and CD2 were expressed in 10, 7, and 5 patients, respectively. Of the 14 patients with inv(16), 13 expressed CD13, 11 expressed CD33, 8 expressed CD34, 5 expressed CD14, 3 expressed CD7, and 3 expressed CD2. Of the 73 patients with cytogenetic records, 30 (41.1%) had clonal chromosomal abnormalities. The expression of CD2 and CD34 was associated with karyotypic abnormalities. The expression of CD2 was higher in M4Eo patients, with no correlation to inv(16). CONCLUSIONS: Acute myelomonocytic leukemia mainly expresses myeloid lineage antigens. The expression of CD2 and CD34 is correlated to karyotypic abnormalities. The expression of CD2 is higher in M4Eo. Inv(16) exists in 40% of M4 patients and the expression of all the antigens has no correlation to inv(16).

Adolescent↗

[Detection of circulating and bone marrow myeloma cells in patients with multiple myeloma and its clinical significance].

This study was aimed to investigate the correlation between circulating myeloma cells (CMC) and bone marrow myeloma cells (MMC) in patients with multiple myeloma (MM) and its clinical significance. Four-color flow cytometry was used to detect the percentage of CMC and MMC in 55 patients with MM. Other prognosis-associated factors such as beta(2) microglobulin (beta(2)-MG), serum albumin (Alb), chromosomal abnormalities and renal function were simultaneously analyzed. The patients were divided into four groups: group A, in which CMC and MMC were simultaneously detected; group B, in which only MMC were detected; group C, in which only CMC were detected; group D, in which no myeloma cells were detected in peripheral blood or bone marrow. The results showed that the concentrations of beta(2)-MG and creatinine were significantly increased and Alb markedly decreased in group A as compared with other groups. Statistical differences existed in the above-mentioned factors between patients with myeloma cells detected and not detected. The percentages of CMC or MMC in newly diagnosed, refractory and relapsed patients were apparently higher than those in patients with partial and complete remission, respectively. CMC were strikingly correlated with MMC. It is concluded that the percentages of CMC and MMC not only imply tumor load in MM patients, but also predict the progression of MM, respectively for patients with MM, in those patients CMC and MMC were simultaneously detected.

Adult↗

[Relationship between leptin gene of adipose tissues and nonalcoholic fatty liver disease].

OBJECTIVE: To investigate leptin mRNA expressions in subcutaneous (SC) and omental (OM) adipose tissues of patients with nonalcoholic fatty liver disease (NAFLD), and their relationships with insulin resistance (IR), blood leptin, blood triglyceride, total blood cholesterol, blood glucose, body weight index and waist-hip ratio. METHODS: SC and OM adipose tissues were obtained from 10 obese and 11 nonobese NAFLD patients and from 11 obese and 13 nonobese patients without NAFLD, who served as controls. Leptin mRNA expression levels in the subcutaneous and omental adipose tissues were measured using SYBR Green I quantitative real-time PCR. IR was estimated using homeostasis assessment (HOMA). The levels of plasma leptin and insulin were measured using ELISA. RESULTS: The relative mRNA expression of leptin, HOMA-IR and blood leptin levels in NAFLD differed significantly from those of the controls (P < 0.05). The leptin/GAPDH ratio of the obese and nonobese NAFLD and control cases were 1.32 +/- 0.12, 0.99 +/- 0.05, 1.10 +/- 0.09, 0.87 +/- 0.13 respectively. The expression levels of SC and OM adipose leptin mRNA in NAFLD patients were positively correlated with HOMA-IR (r=0.72, P < 0.05), blood leptin (r=0.69, P < 0.05), blood triglyceride (r=0.32, P < 0.05), body weight index (r=0.57, P < 0.05) and waist-hip ratio (r=0.50, P <0.05). CONCLUSION: The primary reason for high levels of blood leptin is high leptin mRNA expression in adipose tissues; in both obese and nonobese patients with NAFLD; high levels of blood leptin and the leptin mRNA expression in adipose tissues and IR exist. These findings suggest that leptin resistance exists in patients with NAFLD and leptin resistance is positively correlated with NAFLD, the same as in insulin resistance.

Adipose Tissue↗

[Karyotype analysis in 119 patients with chronic myeloid leukemia at blast crisis].

To investigate the karyotype of chronic myeloid leukemia in blast crisis (CML-BC), karyotype analysis was performed with R-banding technique in 119 patients with CML-BC. Dual fusion fluorescence in situ hybridization (FISH) was used to detect derivative chromosome 9 deletions in randomly selected 28 cases of them. The results showed that 11 cases (8.9%) were Ph negative; 113 cases (91.1%) were Ph positive; 104 cases (83.9%) had standard Ph translocation; 9 cases (7.2%) showed variant translocation, including 4 cases (3.2%) with simple variant translocation and 5 cases (4.0%) with complex variant translocation. 72.6% of Ph negative CML-BC had extra chromosomal abnormalities, with the most common ones being i (17q) and +14. 72.3% of Ph positive CML-BC had extra cytogenetic changes and +Ph, +8, i (17q) were the most frequent. The average time between diagnosis and blast crisis was 29.0 months (range 2 to 66 months) for Ph negative cases and 34.2 months (range 1 to 127 months) for Ph positive cases. 5 cases (5/28, 17.9%) with der (9) deletions were detected by FISH technique. It is concluded that extra chromosomal abnormalities are common in CML-BC patients and FISH can effectively detect the der (9) deletions.

Adult↗

Deaggregation behavior of the phenol gemini derivatives.

The phenol gemini compounds were synthesized by rebuilding the substituents and lateral chain on the phenyl ring. Two parts of the molecules were connected by a spacer of hydrocarbon chain via ester groups. The deaggregation behaviors of target molecules were investigated by studying coaggregation behaviors, evaluating the deaggregating abilities in terms of fluorescence measurements, the measurements of their aggregation number and the effects on restraining the cell adhesion. In present cases, all of these experiments give the same results; that is, in these molecules, the longer branched methyl hydrocarbon chain and the combination of methoxy with hydroxyl groups on the phenyl ring possess the higher deaggregating abilities in the studied situation. The molecules with two hydrocarbon chains, i.e., the phenol gemini compounds, are more effective to deaggregate the aggregated probes than the molecules with one hydrocarbon chain. To find an effective deaggregator might be helpful to design the medicine for the cure of arteriosclerosis.

Journal Article↗