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Biomedical subjects

Yang Li

Publications and source records attributed to Yang Li.

At least 55 records · Page 3Linked to original sources

Catalpol modulates the expressions of Bcl-2 and Bax and attenuates apoptosis in gerbils after ischemic injury.

Our previous study described the neuroprotective effects of catalpol in gerbil ischemic model, in which catalpol was shown to prevent hippocampal neurons from death and ameliorate the cognitive ability of the animals. In the study, we focused on investigating the neuroprotective mechanism of catalpol. Animals were randomly assigned three groups as sham-operated, ischemia-treated with saline and ischemia-treated with catalpol. Transient global ischemia was produced by a 5 min occlusion of the bilateral common carotid arteries. Catalpol was intraperitoneally injected at the dose of 5 mg/kg immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h. Histology as well as immunohistochemistry and TUNEL (the terminal deoxynucleotidyl transferase-mediated UTP nick end label) analysis were performed on serial slices through the dorsal hippocampus after gerbils were sacrificed. The results showed that 5 min transient global ischemia followed by 4 days reperfusion caused significant increases in TUNEL-positive and Bax-positive cells in hippocampal CA1 subfield. Catalpol not only significantly reduced TUNEL-positive and Bax-positive cells but also significantly increased Bcl-2-positive cells. All these suggested that catalpol could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.

Animals↗

The heat shock protein 90 inhibitor 17-AAG induces cell cycle arrest and apoptosis in mantle cell lymphoma cell lines by depleting cyclin D1, Akt, Bid and activating caspase 9.

Mantle cell lymphoma (MCL), a distinct type of non-Hodgkin lymphoma, is characterised by the overexpression of cyclin D1. Heat shock protein 90 (HSP90) is a molecular chaperon to proteins that regulate cell cycle and survival. 17-allylamino-17-demethoxy-geldanamycin (17-AAG), a HSP90 small molecule inhibitor, induced G(0/1) cell cycle arrest and cell death in a dose- and time-dependent manner in MCL cell lines. This effect was associated with the downregulation of cyclin D1, cdk4 and Akt, depletion of Bid, and activation of the intrinsic/mitochondrial caspase pathway. These data suggest that 17-AAG may have a potential therapeutic value in patients with MCL.

Antineoplastic Agents↗

An optimal pooling strategy applied to high-throughput screening for rare marker-free transformants.

An optimal pooling system, called Accurate and Fast Target Screening, has been developed for high-throughput identifying the rare marker-free transformants. This system can identify targets between 10- and 100-fold more efficiently than analysis of individual samples. By calculating the efficiency for different proportions of targets and the optimal group size in a worst case scenario, we are able to estimate an upper limit for the number of tests that are required. The application of this system to determine the transgene in an artificially constructed population of transgenic and non-transgenic wheat lines successfully identified the 10 positive samples located randomly with 990 negative samples using only 92 PCR reactions. The same approach was also applied to determine transgene expression by SDS-PAGE of seed proteins. This system gives unambiguous positive or negative results and should facilitate marker-free transformation.

Algorithms↗

Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.

Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify beta-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.

Animals↗

Effects of lip repair on maxillary growth and facial soft tissue development in patients with a complete unilateral cleft of lip, alveolus and palate.

PURPOSE: To examine the relationship between lip repair and inhibition of maxillary growth, and to investigate the characteristics of upper lip in patients with complete unilateral clefts of lip, alveolus and palate. MATERIAL AND METHODS: Lateral cephalometric radiographs and photographs (anterior-posterior and profile) were taken for 3 groups of patients: (1) 35 complete unilateral cleft lip, alveolus and palate cases in whom only a labioplasty was performed as infants; (2) 47 cases who had both lip and palate repaired; and (3) 37 non-cleft peers as controls. RESULTS: There was maxillary retrusion in groups (1) and (2). Surface area and height of the upper lip was reduced in both these groups when compared with the normal controls. CONCLUSION: Lip repair is a most important factor in the restraint of maxillary growth in patients with complete unilateral clefts of lip, alveolus and palate. And height and projection of the upper lip are reduced following lip repair.

Adolescent↗

The preparation and characterisation of hetero- and homobimetallic complexes containing bridging naphthalene-1,8-dithiolato ligands.

Homo- and heterobimetallic complexes of the form [(PPh(3))(2)(mu(2)-1,8-S(2)-nap){ML(n)}] (in which (1,8-S(2)-nap)=naphtho-1,8-dithiolate and {ML(n)}={PtCl(2)} (1), {PtClMe} (2), {PtClPh} (3), {PtMe(2)} (4), {PtIMe(3)} (5) and {Mo(CO)(4)} (6)) were obtained by the addition of [PtCl(2)(NCPh)(2)], [PtClMe(cod)] (cod=1,5-cyclooctadiene), [PtClPh(cod)], [PtMe(2)(cod)], [{PtIMe(3)}(4)] and [Mo(CO)(4)(nbd)] (nbd=norbornadiene), respectively, to [Pt(PPh(3))(2)(1,8-S(2)-nap)]. Synthesis of cationic complexes was achieved by the addition of one or two equivalents of a halide abstractor, Ag[BF(4)] or Ag[ClO(4)], to [{Pt(mu-Cl)(mu-eta(2):eta(1)-C(3)H(5))}(4)], [{Pd(mu-Cl)(eta(3)-C(3)H(5))}(2)], [{IrCl(mu-Cl)(eta(5)-C(5)Me(5))}(2)] (in which C(5)Me(5)=Cp*=1,2,3,4,5-pentamethylcyclopentadienyl), [{RhCl(mu-Cl)(eta(5)-C(5)Me(5))}(2)], [PtCl(2)(PMe(2)Ph)(2)] and [{Rh(mu-Cl)(cod)}(2)] to give the appropriate coordinatively unsaturated species that, upon treatment with [(PPh(3))(2)Pt(1,8-S(2)-nap)], gave complexes of the form [(PPh(3))(2)(mu(2)-1,8-S(2)-nap){ML(n)}][X] (in which {ML(n)}[X]={Pt(eta(3)-C(3)H(5))}[ClO(4)] (7), {Pd(eta(3)-C(3)H(5))}[ClO(4)] (8), {IrCl(eta(5)-C(5)Me(5))}[ClO(4)] (9), {RhCl(eta(5)-C(5)Me(5))}[BF(4)] (10), {Pt(PMe(2)Ph)(2)}[ClO(4)](2) (11), {Rh(cod)}[ClO(4)] (12); the carbonyl complex {Rh(CO)(2)}[ClO(4)] (13) was formed by bubbling gaseous CO through a solution of 12. In all cases the naphtho-1,8-dithiolate ligand acts as a bridge between two metal centres to give a four-membered PtMS(2) ring (M=transition metal). All compounds were characterised spectroscopically. The X-ray structures of 5, 6, 7, 8, 10 and 12 reveal a binuclear PtMS(2) core with PtM distances ranging from 2.9630(8)-3.438(1) A for 8 and 5, respectively. The napS(2) mean plane is tilted with respect to the PtP(2)S(2) coordination plane, with dihedral angles in the range 49.7-76.1 degrees and the degree of tilting being related to the PtM distance and the coordination number of M. The sum of the Pt(1)coordination plane/napS(2) angle, a, and the Pt(1)coordination plane/M(2)coordination plane angle, b, a+b, is close to 120 degrees in nearly all cases. This suggests that electronic effects play a significant role in these binuclear systems.

Journal Article↗

Further errors in polymorph identification: furosemide and finasteride.

Reassessment of the reported single-crystal X-ray diffraction characterization of polymorphs of furosemide and finasteride shows that, in each case, incomplete data collections have resulted in the mistaken identification of two forms that are, in fact, identical.

Crystallography, X-Ray↗

[Effects of different catheter ablation strategies in treatment of typical atrial flutter complicated with paroxysmal atrial fibrillation].

OBJECTIVE: To evaluate the clinical effects of different catheter ablation strategies in the treatment of typical atrial flutter complicated with paroxysmal atrial fibrillation (PAF). [CTIA, pulmonary vein segmental isolation (PVSI), CTIA + PVI] to the patients coexisted with typical atrial flutter and PAF. METHODS: 66 patients with typical atrial flutter complicated with PAF were divided into 3 groups: Group A (n = 30), undergoing cavotricuspid isthmus ablation, (CTIA), Group B (n = 17), undergoing pulmonary vein segmental isolation, (PVSI), and Group C (n = 19), undergoing CTIA + PVSI. Follow-up was conducted for 30.5 weeks +/- 10.4 weeks. The clinical curative effects, operation safety, and complication were evaluated. RESULTS: The recurrence rate of typical atrial flutter within 12 weeks after operation of Groups A and C were 13.3% and 10.5% respectively, both significantly lower than that of Group B (52.9%, both P < 0.05) without no significant difference between Group A and Group C (P > 0.05). The recurrence rate of typical atrial flutter within 36 weeks after operation of the Groups A, B, and C were 10%, 11.8%, and 10.5% respectively, without significant differences among these 3 groups (all P > 0.05). The recurrence rates of PAF within 12 weeks and 30 weeks after operation of Groups B and C were 29.4% and 31.6%, and 23.5% and 26.3% respectively, all significantly lower than those of Group A (46.7% and 73.3% respectively, all P < 0.05) without significant o differences between Groups B and C. CONCLUSION: In patients with both typical atrial flutter and PAF, pure CTIA has a good effect on typical atrial flutter, whereas the PAF recurrence rate is higher; Pure PVSI has a good control of typical atrial flutter while curing PAF; PVSI + CTIA only reduces the early recurrence of typical atrial flutter, however, has no advantage in long-term follow up.

Adult↗

Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration.

Migration of activated macrophages is essential for resolution of acute inflammation and the initiation of adaptive immunity. Here, we show that efficient macrophage migration in inflammatory environment depends on Mac-1 recognition of a binary complex consisting of fibrin within the provisional matrix and the protease tPA (tissue-type plasminogen activator). Subsequent neutralization of tPA by its inhibitor PAI-1 enhances binding of the integrin-protease-inhibitor complex to the endocytic receptor LRP (lipoprotein receptor-related protein), triggering a switch from cell adhesion to cell detachment. Genetic inactivation of Mac-1, tPA, PAI-1 or LRP but not the protease uPA abrogates macrophage migration. The defective macrophage migration in PAI-1-deficient mice can be restored by wild-type but not by a mutant PAI-1 that does not interact with LRP. In vitro analysis shows that tPA promotes Mac-1-mediated adhesion, whereas PAI-1 and LRP facilitate its transition to cell retraction. Our results emphasize the importance of ordered transitions both temporally and spatially between individual steps of cell migration, and support a model where efficient migration of inflammatory macrophages depends on cooperation of three physiologically prominent systems (integrins, coagulation and fibrinolysis, and endocytosis).

Animals↗

Characterization of RNA in saliva.

BACKGROUND: We have previously shown that human mRNAs are present in saliva and can be used as biomarkers of oral cancer. In this study, we analyzed the integrity, sources, and stability of salivary RNA. METHODS: We measured the integrity of salivary RNA with reverse transcription followed by PCR (RT-PCR) or RT-quantitative PCR (RT-qPCR). To study RNA entry sites into the oral cavity, we used RT-PCR analysis of salivary RNA from the 3 major salivary glands, gingival crevice fluid, and desquamated oral epithelial cells. We measured stability of the salivary beta-actin mRNA by RT-qPCR of salivary RNA incubated at room temperature for different periods of time. We measured RNA association with other macromolecules by filtering saliva through pores of different sizes before performing RT-qPCR. To assess RNA-macromolecule interaction, we incubated saliva with Triton X-100 for different periods of time before performing RT-qPCR. RESULTS: In most cases, we detected partial- to full-length salivary mRNAs and smaller amounts of middle and 3' gene amplicons compared with the 5'. RNA was present in all oral fluids examined. Endogenous salivary beta-actin mRNA degraded more slowly than exogenous beta-actin mRNA, with half-lives of 12.2 and 0.4 min, respectively (P <0.001). Salivary RNA could not pass through 0.22 or 0.45 mum pores. Incubation of saliva with Triton X-100 accelerated degradation of salivary RNA. CONCLUSIONS: Saliva harbors both full-length and partially degraded forms of mRNA. RNA enters the oral cavity from different sources, and association with macromolecules may protect salivary RNA from degradation.

Adult↗

Concise asymmetric total synthesis of obolactone.

The first efficient asymmetric synthesis of obolactone 1 has been accomplished in 11 steps and with a 15% overall yield in which Brown's enantioselective allylation reactions and ring-closing metathesis reaction are key steps.

Aldehydes↗

Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents.

Current treatments for chronic hepatitis B virus (HBV) infection include the use of interferon-alpha and of nucleoside analogs lamivudine, adefovir and entecavir. However, the use of interferon-alpha has many side effects while that of nucleosidic inhibitors can lead to the emergence of resistant viruses. Hence, new drugs for the treatment of HBV infection are still highly desired. Oxadiazoles have been observed to exhibit antiviral activities against RNA viruses. In this study, a facile synthesis of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles is reported. The compounds were then evaluated for their anti-HBV activity. 1-[2-[5-(1-Benzenesulfonyl-propyl)-[1,3,4]oxadiazol-2-yl-sulfanyl]-ethyl]-4-(2-methoxy-phenyl)-piperazine (1i) was able to inhibit the expression of the viral antigens, HBsAg and HBeAg in a concentration-dependent manner with no cytotoxic effects and without any effects on the expression of viral transcripts. Concentration- and time-dependent reductions in virion production were also observed. The inhibition of virion production was comparable to that of lamivudine and EC(50) values of 1.63 and 2.96 microM were obtained for compound 1i and lamivudine, respectively. Thus, in addition to the antiviral effects on RNA viruses, oxadiazoles also have anti-HBV activities.

Antiviral Agents↗

The novel human gene MIP functions as a co-activator of hMafF.

The human transcription factor MafF (hMafF) lacks a transactivation domain, it contains a heptad-leucine repeat motif (viz., Leu-zipper) that may mediate protein-protein interactions to regulate transcriptional activities. A protein with a coiled-coil domain encoded by a novel human gene (GenBank Accession No. AF289559) was found to interact with hMafF in vitro and in vivo and is designated as a MafF interacting protein (MIP). Here, we provide evidence that the coiled-coil domain of MIP is essential for binding to the Leu-zipper of hMafF and that the interaction between MIP and hMafF causes the translocalization of MIP from cytoplasm to nucleolus in HELA cells. We used a promoter-reporter system containing six tandem repeats of the US2 element, located in the promoter of the human oxytocin receptor gene and reported to bind specifically to hMafF, to understand effects on transcriptional activation of hMafF, and its interaction with MIP. Expression of hMafF or MIP alone did not alter basal reporter transcription activity, whereas co-expression of hMafF and MIP activated transcription efficiently. Moreover, truncated MIP, still containing the coiled-coil domain, transactivated as well as the full-length MIP did, and highlighting that MIP acts as a co-activator of hMafF.

Amino Acid Sequence↗

Serum circulating human mRNA profiling and its utility for oral cancer detection.

PURPOSE: The purpose of this study is to explore the presence of informative RNA biomarkers from human serum transcriptome, and evaluate the serum transcriptome diagnostics for disease detection. Oral squamous cell carcinoma (OSCC) was selected as the proof-of-concept disease. PATIENTS AND METHODS: Blood samples were collected from patients (n = 32) with primary T1/T2 OSCC and matched healthy patients (n = 35). Circulating RNA was isolated from serum and linearly amplified using T7 polymerase. Microarrays were applied for profiling transcriptome in serum from 10 cancer patients and controls. The differential gene expression was analyzed by combining the present calls, t tests, and fold-change statistics. Quantitative polymerase chain reaction (PCR) was used to validate the selected candidate RNA markers identified by microarray. Receiver operating characteristic curve and classification models were exploited to evaluate the diagnostic power of these markers for OSCC. RESULTS: Human serum circulating mRNAs were presented by reverse transcriptase PCR. Microarray identified 2,623 +/- 868 probes assigned present calls in OSCC (n = 10) versus 1,792 +/- 165 in healthy patients (n = 10), indicating a higher complexity of serum transciptome in OSCC patients (P = .002, Wilcoxon test). Three hundred thirty-five serum RNAs exhibited significantly differential expression level between the two groups (P < .05, t test; fold > or = 2). Five cancer-related gene transcripts were consistently validated by quantitative PCR on serum from OSCC patients (n = 32) and controls (n = 35). The best combination of biomarkers yielded a receiver operating characteristic curve value of 88%, sensitivity (91%), and specificity (71%) in distinguishing OSCC. CONCLUSION: The utility of serum transcriptome diagnostics is successfully demonstrated for OSCC detection. This novel concept could be developed as an adjunctive tool for disease diagnosis.

Biomarkers↗

The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-kappaB) in endotoxic shock.

To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide (LPS), we studied the effects of endotoxic shock on rat brain cortex NF-kappaB and the effects of dexamethasone on these changes. Rats were randomly divided into LPS, LPS + dexamethasone, and control groups. The DNA-binding activity of NF-kappaB was observed using electrophoretic mobility shift assay (EMSA). Protein expression in nuclear extracts was studied using Western blots, and nuclear translocation was observed using immunohistochemistry. These indices were assayed at 1 h and 4 h after intravenous injection of LPS (4 mg x kg(-1)). EMSA showed significantly increased NF-kappaB DNA-binding activity in nuclear extracts from the LPS group at both 1 h and 4 h after LPS injection, compared with the control group (P < 0.01). For the LPS group, the NF-kappaB DNA-binding activity was greater at 1 h than at 4 h (P < 0.05). The expression of p65 and p50 protein in the nuclear extracts was also increased, as compared with the control group. However, the expression of p65 and p50 protein from cytosolic extracts did not show any significant change. Dexamethasone down-regulated not only NF-kappaB DNA-binding activity but also the expression of p65 protein in the nuclear extracts. From these data, we have concluded that NF-kappaB activation and nuclear translocation of NF-kappaB play a key role in the molecular mechanism of brain tissue injury in endotoxic shock. Dexamethasone may alleviate brain injury by inhibiting NF-kappaB activation.

Animals↗

SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase.

Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochemical potency have been identified which are selective for the inhibition of HCV NS5b over other polymerases. The structures of the complexes formed between several of these inhibitors and HCV NS5b were determined by X-ray crystallography, and the inhibitors were found to bind in an allosteric binding site separate from the active site. Structure-activity relationships and structural studies have identified the mechanism of action for compounds in this series, several of which possess drug-like properties, as unique, reversible, covalent inhibitors of HCV NS5b.

Allosteric Site↗

Synaptic release of zinc from brain slices: factors governing release, imaging, and accurate calculation of concentration.

Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We present original data on four of the issues and review published data on two others. We show that common errors can cause up to a 3000-fold underestimation of the concentration of released zinc. The results should help bring consistency to the study of synaptic release of zinc.

Animals↗