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Biomedical subjects

He Zhao

Publications and source records attributed to He Zhao.

12 recordsLinked to original sources
PubMed2026

Diverse haplotypes at a complex Solanum americanum locus confer resistance to Phytophthora infestans and P. capsici.

Plants encounter diverse pathogens and have evolved a two-layered innate immune system to detect pathogen molecules and activate defense mechanisms that restrict infection. Most cloned plant Resistance (R) genes encode NLR immune receptors. NLR genes are often found in clusters of paralogs with sequence and copy number variation; whether these NLR clusters evolve in response to single or multiple pathogens has been unclear. We report here the isolation of a Phytophthora capsici resistance gene, Rpc2, along with a novel P. infestans resistance gene, Rpi-amr5, from two Solanum americanum accessions. These orthologous genes reside in the Rpi-amr1 cluster, which has previously been associated with resistance to P. infestans. By screening RXLR effector libraries of P. infestans and P. capsici, we identified multiple effectors recognised by both NLRs. Our findings highlight the complexity of NLR clusters and evolution driven by interactions with multiple pathogens. This work will underpin efforts to elevate resistance against Phytophthora pathogens and enhances our understanding of NLR evolution.

Journal Article↗
PubMed2005

Estimation of time-varying coherence function using time-varying transfer functions.

We introduce a new method to estimate reliable time-varying coherence functions (TVCF) for causal systems. The technique is based on our previously developed method to estimate time-varying transfer functions (TVTF), known as the time-varying optimal parameter search algorithm [Zou, R., H. Wang, and K. H. Chon. A robust time-varying identification algorithm using basis functions. Ann. Biomed. Eng. 31: 840-853, 2003]. The TVCF is estimated by the multiplication of two TVTFs. The two TVTFs are obtained using signal x as the input and signal y as the output to produce the first TVTF, and signal y as the input and signal x as the output to produce the second TVTF. Demonstration of the feasibility and efficacy of the proposed approach is provided with both simulation examples and application to renal blood flow and pressure data. The proposed approach provides higher time-frequency resolution TVCF than afforded by the short time Fourier transform based TVCF.

Animals↗
PubMed2005

Multiple time-varying dynamic analysis using multiple sets of basis functions.

We extend a recently developed algorithm that expands the time-varying parameters onto a single set of basis functions, to multiple sets of basis functions. This feature allows the capability to capture many different dynamics that may be inherent in the system. A single set of basis functions that has its own unique characteristics can best capture dynamics of the system that have similar features. Therefore, for systems that have multiple dynamics, the use of a single set of basis functions may not be adequate. Computer simulation examples do indeed show the benefit of using multiple sets of basis functions over the single set of basis functions for cases with many switching dynamics. Moreover, the proposed method remains accurate even under significant noise contamination. Application of the proposed approach to blood pressure data likewise indicate better tracking capability of the two sets of basis function than the recursive least squares or a single set of basis functions.

Algorithms↗
PubMed2003

1H-Pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes: a unique structural class of dopamine D4 selective ligands.

A series of novel 1H-pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes was prepared and screened at selected dopamine receptor subtypes. Compound 4 (NGB 4420) displayed high affinity and selectivity (>100-fold) for the D(4) over D(2) and other CNS receptors. This compound was identified as a D(4) antagonist via its attenuation of dopamine agonist-induced GTPgamma(35)S binding at D(4) receptor.

Dopamine Antagonists↗
PubMed2003

Design, synthesis, and discovery of 5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives: a novel series of mixed dopamine D2/D4 receptor antagonist.

5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives were designed, synthesized, and identified as a new series of mixed dopamine D(2)/D(4) receptor antagonists. This series featured a rigid tricyclic ring system as an important pharmacophore core structure for high binding affinity. Molecular modeling studies are also described.

Dopamine D2 Receptor Antagonists↗
PubMed2002

Metal-dependent inhibition of HIV-1 integrase.

Human immunodeficiency virus type 1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Therefore, IN inhibitors are being sought for chemotherapy against AIDS. We had previously identified a series of salicylhydrazides as potent inhibitors of IN in vitro (Neamati, N.; et al. J. Med. Chem. 1998, 41, 3202-3209.). Herein, we report the design, synthesis, and antiviral activity of three novel mercaptosalicylhydrazide (MSH) derivatives. MSHs were effective against the IN catalytic core domain and inhibited IN binding to HIV LTR DNA. They also inhibited catalytic activities of IN in IN-DNA preassembled complexes. Site-directed mutagenesis and molecular modeling studies suggest that MSHs bind to cysteine 65 and chelate Mg(2+) at the active site of HIV-1 IN. Contrary to salicylhydrazides, the MSHs are 300-fold less cytotoxic and exhibit antiviral activity. They are also active in Mg(2+)-based assays, while IN inhibition by salicylhydrazides is strictly Mn(2+)-dependent. Additionally, in target and cell-based assays, the MSHs have no detectable effect on other retroviral targets, including reverse transcriptase, protease, and virus attachment, and exhibit no detectable activity against human topoisomerases I and II at concentrations that effectively inhibit IN. These data suggest that MSHs are selective inhibitors of HIV-1 IN and may serve as leads for antiviral therapeutics.

Antiviral Agents↗
PubMed2002

Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 1: identification and structure-activity relationships.

Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 7b. Their related synthesis was also reported.

Animals↗
PubMed2002

Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 2: asymmetric synthesis and biological evaluation.

A series of chiral benzylpiperazinyl-1-(2,3-dihydro-indol-1-yl)ethanone derivatives were prepared and examined for their affinity at dopamine D(2) and D(4) receptors. Three compounds having D(2)/D(4) affinity ratios approximating that found for the atypical neuroleptic clozapine were further evaluated in behavioral tests of antipsychotic efficacy and motor side effects.

Amphetamine↗
PubMed2002

Diet-related factors, educational levels and blood pressure in a Chinese population sample: findings from the Japan-China Cooperative Research Project.

As part of the Japan-China Cooperative Research Project of the WHO-Cardiovascular Disease and Alimentary Comparison Study, a cross-sectional study was carried out to investigate risk factors for high blood pressure (BP) in male adults in Chongqing, China. Subjects with hypertension (HT) were defined as those if they had systolic BP (SBP) > or = 140 mmHg or diastolic BP (DBP) > or = 90 mmHg or if they were receiving anti-hypertensive drug therapy. Subjects were also categorized into three groups according to their level of education, i.e., low- (< or = 6 years), intermediate- (7-9 years), or high- (> or = 10 years) level education. The results were as follows. (a) 20.3% of subjects had HT, 16.7% had hypercholesterolemia (serum total cholesterol > or = 220 mg/dl), and 23.4% were overweight (body mass index > or = 25 kg/m2). (b) After adjustment for age, SBP and DBP showed a significant positive association with body mass index, urinary sodium (Na) excretion, and total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio (TC/HDL). SBP and DBP tended to be negatively associated with 24 h urinary potassium (K) and magnesium (Mg) excretion. (c) Subjects with the highest educational level had the lowest prevalence of HT (11.6%), followed by those with the low (22.6%) and the intermediate (25.0%) educational levels (p<0.05). (d) Logistic regression analysis indicated that the relative risks (95%CI) of being overweight, high TC/HDL ratio, high Na excretion and lower educational level (<10 years) for risk of HT were 5.39 (2.42-11.98), 1.73 (1.13-2.63), 1.30 (1.06-1.58), and 2.56 (1.41-6.71) respectively. (e) Subjects with the highest educational level had significantly lower Na, significantly lower Na/K ratio excretion, and significantly higher K and Mg excretion values than those with intermediate or low educational levels. In conclusion, BP was strongly associated with BMI, salt intake and other diet-related factors in the study sample. The results emphasize that education plays an important role in public health for the control of high BP in the Chinese population.

Adult↗
PubMed2002

Effects of tetracycline-controlled antisense bcl-2 expression on the growth and apoptosis of human neuroblastoma cell line SK-N-MC.

OBJECTIVE: To study the effects of tetracycline-controlled antisense bcl-2 expression on the growth and apoptosis of human neuroblastoma cell line SK-N-MC and the related mechanisms. METHODS: The tetracycline-controlled antisense bcl-2 expressing vector PUCCOMB1(CMV)/Asbcl-2 was constructed by inserting a 0.6 kb fragment antisense bcl-2 cDNA sequence into the plasmid PUCCOMB1(CMV). SK-N-MC cells were transfected with PUCCOMB1(CMV)-Asbcl-2 or PUCCOMB1(CMV) by Lipofectamine( trade mark ). The transfectant cells were further studied for growth viability and apoptosis induced by antisense bcl-2 expression controlled by tetracycline. The expression of bcl-x(L)/bcl-x(S) mRNA was examined by RT-PCR and the changes of expression of proteins caspase-3, bcl-2 and PARP were examined by Western-blot. RESULTS: The cell viability of the antisense bcl-2 transfected cells decreased significantly, and the apoptotic cells and DNA ladder could be found earlier in the antisense bcl-2 cells than in the empty vector transfected cells. We also found a decrease of non-activated caspase-3, cleavages of PARP and bcl-2 protein after treatment without fetal bovine serum (FBS) by Western-blot, but there was no change in the expression of bcl-x(L)/bcl-x(S) mRNA examined by RT-PCR during apoptosis. CONCLUSIONS: The results suggested that tetracycline-controlled expression of antisense bcl-2 can effectively inhibit the cell viability of SK-N-MC cells, increase the sensitivity to apoptosis-inducing factor, as well as facilitate cell apoptosis after treatment of culture without FBS. Except bcl-x(L)/bcl-x(S) mRNA expression, activation of caspase-3, cleavage of protein PARP and bcl-2 were all associated with apoptosis.

Apoptosis↗