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Biomedical subjects

Bin Yang

Publications and source records attributed to Bin Yang.

At least 91 records · Page 5Linked to original sources

Direct asymmetric synthesis of beta-amino ketones from sulfinimines (N-sulfinylimines). Synthesis of (-)-indolizidine 209B.

N-Sulfinyl beta-amino ketones, prepared directly from the potassium enolates of methyl ketones and enantiopure sulfinimines, are transformed in one pot to protected amino ketones, which are valuable chiral building blocks for the assembly of piperidines. The utility of this methodology is illustrated in a concise asymmetric synthesis of (-)-indolizidine 209B. [reaction: see text]

Alkaloids↗

[Microinjection of L-NAME into dorsal raphe nucleus inhibits nociceptive response in sigmoid pain model of rats].

By means of Fos immunocytochemistry, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and microinjection methods, the role of nitric oxide synthase (NOS) of dorsal raphe (DR) neurons in the modulation of rats sigmoid pain was studied. The results showed: (1) Rats exhibited aversive behavioral responses related to visceral pain after injecting formalin into the sigmoid wall. NOS neurons in DR were up-regulated, in addition, about 8% of NOS-labeled neurons were Fos positive. By contrast, there were no Fos/NOS double-labeled neurons in the control group. (2) Formalin-induced sigmoid pain scores and the expression of Fos in the spinal cord at S1 segment were decreased after microinjecting L-NAME into the DR. These findings suggest that NOS neurons are involved in the modulation of formalin-induced sigmoid pain and that NO may play an important role in the transmission of visceral nociceptive message in the midbrain.

Analgesics↗

Rev binds specifically to a purine loop in the SL1 region of the HIV-1 leader RNA.

The leader RNA sequence of human immunodeficiency virus type 1 (HIV-1) consists of a complex series of stem loop structures that are critical for viral replication. Three-dimensional structural analysis by NMR of one of these structures, the SL1 stem loop of the packaging signal region, revealed a highly conserved purine rich loop with a structure nearly identical to the Rev-binding loop of the Rev response element. Using band-shift assays, surface plasmon resonance, and further NMR analysis, we demonstrate that this loop binds Rev. HIV-1 appears to have a second Rev-binding site close to the major splice donor site that may have an additional role in the viral life cycle.

5' Untranslated Regions↗

The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA.

High mutation frequency during reverse transcription has a principal role in the genetic variation of primate lentiviral populations. It is the main driving force for the generation of drug resistance and the escape from immune surveillance. G to A hypermutation is one of the characteristics of primate lentiviruses, as well as other retroviruses, during replication in vivo and in cell culture. The molecular mechanisms of this process, however, remain to be clarified. Here, we demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G; APOBEC3G), an endogenous inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is able to induce G to A hypermutation in newly synthesized viral DNA. This effect can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that this viral DNA mutator is a viral defence mechanism in host cells that may induce either lethal hypermutation or instability of the incoming nascent viral reverse transcripts, which could account for the Vif-defective phenotype. Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations.

APOBEC-3G Deaminase↗

Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, but the molecular mechanisms of hepatocarcinogenesis remain unclear. Although p53 mutations are frequently observed in Asian HCC, it is not a common event in Western HCC. Recent studies suggest that tumor suppressor genes (TSGs) can also be silenced through epigenetic disruption, such as promoter CpG island methylation, during carcinogenesis. To further understand the molecular mechanism of hepatocarcinogenesis, we have investigated the promoter methylation status of nine TSGs (SOCS-1, GSTP, APC, E-cadherin, RAR-beta, p14, p15, p16, and p73) in 51 cases of HCC using methylation-specific polymerase chain reaction. We found that 82% of HCCs had methylation of at least one TSG promoter. The most frequently methylated TSGs in HCC were: SOCS-1 (65%), GSTP (54%), APC (53%), E-cadherin (49%), and p15 (49%). Methylation of SOCS-1, GSTP, APC, E-cadherin, and p15 was more frequent in HCC than in nontumor liver (P < 0.05). Methylation of SOCS-1, GSTP, and p15 was also significantly more frequent in HCC than cirrhotic liver (P < 0.05). Although methylation of one or two genes could be seen in both nontumor and cirrhotic livers, 53% of the HCC cases had three or more TSG promoters methylated, in comparison to 0% in nontumor liver and 13% in cirrhosis (P = 0.001). Methylation of SOCS-1, APC, and p15 was more frequently seen in hepatitis C virus-positive HCC than hepatitis C virus/hepatitis B virus-negative HCC. Our data suggest that promoter hypermethylation of TSGs is a common event in HCC and may play an important role in hepatocarcinogenesis.

Adult↗

Effects of caspase inhibition on the progression of experimental glomerulonephritis.

BACKGROUND: Caspase-3 has a central role in the execution of apoptosis. In a nephrotoxic nephritis (NTN) model, we previously demonstrated an up-regulation of caspase-3 that was associated with inappropriate renal apoptosis, inflammation, tubular atrophy, and renal scarring. METHODS: We applied a pan caspase inhibitor, Boc-Asp (OMe)-fluoro-methyl-ketone (B-D-FMK), directly to rat NTN kidney using an intrarenal cannula fed from an osmotic pump. Animals were treated either for the first 7 days (acutely) to determine the effects on renal inflammation (ED-1 staining) and apoptosis (in situ end labeling of fragmented DNA), or for 28 days commencing 15 days after NTN (chronically) to observe the effects on cell death and renal fibrosis. Changes of caspase-3 and caspase-1 activity were detected by fluorometric substrate cleavage assay. Changes in caspase-3 and caspase-1, interleukin-1 beta (IL-1 beta), and collagen I, III, and IV proteins and mRNA were detected by Western blotting and Northern blotting, respectively. RESULTS: In both treated groups, caspase-3 activity was inhibited, and 17 and 24 kD active caspase-3 proteins were reduced significantly. A compensatory increase of caspase-3 mRNA occurred in the acutely treated group, but decreased in the chronically treated group (P < 0.05). Although there were no significant changes in caspase-1 activity and its active protein, the observed decrease in its precursor in the chronic group was increased by treatment (P < 0.05). Further, IL-1 beta precursor and its mRNA were significantly reduced by treatment only in the chronically treated group. Apoptosis was decreased in the glomeruli of acutely treated rats, and in the tubules and interstitium of chronically treated animals (P < 0.05). Glomerular inflammation was decreased only in the acutely treated group, whereas tubulointerstitial inflammation was lowered in both treated groups (P < 0.05). Glomerulosclerosis was reduced in both inhibitor groups, with a reduction in tubulointerstitial fibrosis and collagen I, III, and IV mRNA restricted to chronically treated animals (P < 0.05). Proteinuria was significantly decreased with caspase inhibition in both treated groups, but not serum creatinine level. CONCLUSION: This study clearly indicates that caspase inhibition reduces renal apoptosis, ameliorates inflammation and fibrosis, and improves proteinuria in experimental glomerulonephritis, which may mainly be related to changes in the caspase enzymatic system.

Amino Acid Chloromethyl Ketones↗

A novel competitive ELISA for both free and protein-bound nitrotyrosine.

3-Nitro-L-tyrosine (nitrotyrosine) has recently been considered to be useful as a biomarker of endogenous production of several reactive nitrogen species including peroxynitrite. In the present study, nitrotyrosine was coupled to human serum albumin (HSA) using a two-step glutaraldehyde method and immunized mouse with multifocal intradermal injections. Using a conventional immunization protocol, 12 stable monoclonal antibodies (MAbs) producing cell lines recognizing nitrotyrosine were obtained. Six MAbs were selected for further characterization. A study of cross-reactions with nitrotyrosine-like compounds showed that the antibodies had a high specificity for nitrotyrosine, but no detectable reactivity with L-tyrosine, p-nitro-L-phenylalanine, o-phospho-L-tyrosine or 3-amino-L-tyrosine. Using these high titer and affinity antibodies, a competitive inhibition ELISA was developed with a lower detection limit of approximately 20 nmol/L to detect both free and protein-bound nitrotyrosine in biological systems.

Animals↗

[The roles of VEGF and C-myc in occurrence, development and metastasis of gallbladder carcinoma].

To investigate the relationship of the expression of vascular endothelial growth factor (VEGF) and C-myc with the occurrence, development and metastasis of gallbladder carcinoma, the expression levels of VEGF and C-myc in gallbladder carcinoma tissue (n = 30) and in normal gallbladder tissue (n = 20) were examined by immunochemistry. Results show that the positive rates of VEGF and C-myc in gallbladder carcinoma tissue were 80% and 63.3% respectively, and 45% and 25% respectively in normal gallbladder tissue. The positive rates of VEGF and C-myc were significantly higher in gallbladder carcinoma than in normal gallbladder tissue. The expression of VEGF and C-myc in gallbladder carcinoma related to the metastasis of gallbladder carcinoma. VEGF and C-myc play important roles in the occurrence, development and metastasis of gallbladder carcinoma.

Adult↗

[Preparation and radioimmunoimaging of a monoclonal antibody against human granulocytes].

The aim of this research is to prepare a novel monoclonal antibody against granulocytes by the intraperitional routine procedure and evaluate the usefulness of (99)Tc(m) labelled anti-granulocyte monoclonal antibody (McAb) SZ-102 for the detection of experimental inflammatory areas in rabbits. It was characterized as IgG1 subclass by the double immunodiffusion analysis. The flow cytometry demonstrated that SZ-102 reacted selectively with human granulocytes, monocytes, and with their bone marrow precursors, while human lymphocytes, red blood cells and platelets remained negative. In addition, SZ-102 antigen was expressed on the macrophages of liver, lung, thymus, spleen and lymph node by immunohistochemical SP methods. It is suggested that McAb SZ-102 is mainly against granulocytes. SZ-102 was labelled with (99)Tc(m) using 2-iminothiolane modification McAb and (99)Tc(m) -glucoheptonate (GH) transchelation method. The experimental rabbit model of inflammatory areas was prepared,through injecting with (99)Tc(m)-SZ-102 by ear-edge vein, and then imaged by SPECT. (99)Tc(m) labelled murine IgG was used as a negative control. The inflammatory areas in rabbits were clearly imaged at 2 to 4 hour after injection of (99)Tc(m)-SZ-102, while the control group after injection of (99)Tc(m)-labeled murine IgG was negative. In conclusion, the McAb SZ-102 may be a potential agent for the diagnosis and localization of inflammatory areas of carcinomas and clinically concealed infectious diseases.

Animals↗

Transient macular edema after laser in-situ keratomileusis.

PURPOSE: To investigate the macular changes induced by laser in situ keratomileusisc (LASIK) procedure. METHODS: Optical Coherence Tomography (OCT) was used to examine 27 eyes of 15 LASIK patients before surgery, and 1 day, 1 week, 1 month after surgery. RESULTS: The mean thickiness of neuroepithelial layer of macula was (195 +/- 24) microns, (178 +/- 16) microns 1 day and 1 month after surgery, respectively, while the baseline was (174 +/- 12) microns. The increase in macular neuroepithelial thickness was correlated with the degree of myopia, but not with the duration of suction or the postoperative BCVA. CONCLUSION: Mild macular edema is common in the first month following LASIK, especially in high myopia. However, no association with loss of BCVA has been established.

Edema↗

Expression of vascular endothelial growth factor and matrix metalloproteinase-2 correlates with the invasion and metastasis of hepatocellular carcinoma.

To investigate the relationship of the expression of vascular endothelial factor (VEGF) and matrix metalloproteinase-2 (MMP-2) with the recurrence and metastasis of hepatocellular carcinoma (HCC), the expression of VEGF and MMP-2 in HCC tissue(n = 50) and in normal liver tissue(n = 30) were examined by immunochemistry. The results showed that the positive rates of VEGF and MMP-2 in HCC tissue were 86% and 60% respectively, and in normal liver tissue were 53.3% and 30% respectively. The positive rates of VEGF and MMP-2 in HCC were significantly higher than those in normal liver tissue. The positive rates of VEGF and MMP-2 in HCC with intra- or extra-hepatic metastasis were higher than those of HCC without metastasis. VEGF and MMP-2 play important roles in the invasion and metastasis of HCC.

Adult↗

[Effect of particle size distribution of dental poly (methyl methacrylate) beads on the microstructure of denture].

OBJECTIVES: To investigate the effect of particle size distribution (PSD) of dental poly (methyl methacrylate) (PMMA) beads on the microstructure of denture. METHODS: It was compared and analyzed that the porosity of three groups of spherical specimens which were made of PMMA beads with different PSD at proper polymer/monomer ratios. And the final microstructure of each group was investigated using Digital High Definition Microscope. RESULTS: With proper polymer/monomer ratio increasing, the occurrence of porosity tended to decrease. The final microstructure of denture varied with PSD of PMMA beads. CONCLUSION: By means of optimizing PSD of beads, the microstructure of denture could be improved, and the occurrence of porosity could be reduced.

Dental Materials↗

[Study of bcl-X(L) protection on retinal photoreceptors from apoptosis in vitro].

OBJECTIVE: To assess the effect of bcl-X(L), an anti-apoptotic gene, on glutamate-induced apoptosis in cultured retinal photoreceptors. METHODS: Glutamate-induced apoptosis in cultured retinal photoreceptors was established. The experiment was divided into three groups: control, glutamate treatment and rAd-gfp-bcl-X(L) + glutamate transfection group, the protection of bcl-X(L) on retinal photoreceptors from apoptosis was evaluated. 6.5 x 10(12) pfu/L rAd-gfp-bcl-X(L) were transfected into retinal photoreceptors in the rAd-gfp-bcl-X(L) + glutamate group 48 h before Glutamate-induced apoptosis was established. The positive photoreceptors with green fluorescence were identified under fluorescence microscopy. The expression of Bcl-X(2) protein in rAd-gfp-bcl-X(L) transfected and non-transfected neurons were assessed by immunohistochemistry assay. DNA fragment was detected by agarose gel electrophoresis. Nuclei were revealed by hoechst33258 staining. RESULTS: rAd-mediated gene delivery can transfect retinal photoreceptors effectively. Increased expression of Bcl-X(L) protein was demonstrated in the rAd-transfecting neurons. Transfection of bcl-X(L) significantly decreased the number of apoptotic retinal photoreceptors in vitro. CONCLUSION: Transfection of bcl-X(L) protects cultured retinal photoreceptors from apoptosis induced by glutamate. Transfection the gene of bcl-X(L) may be a potential gene therapy for retinal degenerative diseases.

Animals↗

[Effect of the biodegradable chitosan external stent on the early changes in the rabbit vein grafts].

OBJECTIVES: To investigate the effect of chitosan biodegradable external stent (CES) on the early changes of rabbit vein graft (VG). METHODS: Rabbit vein grafting models were divided into S group (with perivenous CES) and NS group (without perivenous CES). The VG were harvested in 1 week, 2 weeks, 4 weeks after operation, respectively. The expression of proliferating cell nuclear antigen (PCNA) was used for evaluating the proliferation of the smooth muscle cell (SMC). The thickness, area of neointima and media of the VG were calculated by computer imaging analysis system. RESULTS: CES began to degrade in 2 weeks after operation. The thickness, area of both neointima and media of the VG in S group, increased mildly in 1 week after operation, and kept steady in 1 or 2 weeks after grafting, which was significantly less than NS group (both P < 0.01), then increased mildly in 4 weeks after grafting but still less than NS group (P < 0.05). The expression of PCNA of SMC decreased significantly in comparison with NS group though increasing mildly in four weeks after operation. Both neointimal formation and cell proliferation in the graft wall were significantly reduced by external stenting as compared to the results with unstented grafts. CONCLUSIONS: CES may reduce early intimal and medial hyperplasia, and may be beneficial in improving the long term patency of the VG. The biodegradable characteristics of the CES may influence its effect.

Animals↗