Biomedical subjects

Haiyan Huang

Publications and source records attributed to Haiyan Huang.

17 recordsLinked to original sources

PubMed2026

Efficacy, tolerability, and threshold effect of atropine eye drops for myopia control: A systematic review and dose-response meta-analysis.

Atropine is an emerging therapy for myopia, yet the optimal concentration for prescription remains uncertain. We searched PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Clinical Trials, and ClinicalTrials.gov registry platforms. We included the randomized clinical trials (RCTs) that compared any dose of atropine against a placebo in myopic children. Among 3566 studies assessed, we identified 33 eligible RCTs involving 6301 children aged 4-18 years, with 10 different concentrations and a mean follow-up time of 19.5 ± 12.3 months. A nonlinear relationship was observed between atropine dosage and treatment efficacy (P < 0.001). Compared to placebo groups, the mean differences in reducing annual spherical equivalent refraction progression for atropine concentrations of 0.01%, 0.02%, 0.03%, 0.04%, and 0.05% were 0.21 diopters (D) (95% CI, 0.13-0.28), 0.35 D (95% CI, 0.23-0.46), 0.42 D (95% CI, 0.28-0.56), 0.45 D (95% CI, 0.30-0.60), and 0.46 D (95% CI, 0.32-0.61) respectively For higher concentrations, the estimates were 0.49 D (95% CI, 0.34-0.63) for 0.1% and 0.99 D (95% CI, 0.66-1.31) for 1%, although these were based on fewer and smaller trials. Higher doses of atropine were associated with decreased amplitude of accommodation (P = 0.02), increased pupil diameters (P = 0.01) and a higher frequency of photophobia (P = 0.02). Our findings suggest that the increase in treatment efficacy with higher concentrations may plateau beyond a certain range, and that the current practice of increasing atropine concentrations for children who show inadequate responses to lower doses should be confined to a specific concentration range. This analysis is limited by the number, design heterogeneity, and sample sizes of available trials for higher concentrations, and by the frequent lack of pre-intervention refractive history in included studies. Therefore, estimates-particularly for doses exceeding 0.1%-should be interpreted with caution.

Humans↗

PubMed2006

Transcription profile analyses identify genes and pathways central to root cap functions in maize.

Affymetrix GeneChips arrayed with about one-half (~23K) of the rice genes were used to profile gene transcription activity in three tissues comprising the maize root tip; the proximal meristem (PM), the quiescent center (QC), and the root cap (RC). Here we analyze the gene transcription profile of the RC, compared to both the PM and the QC, from three biological replicates. In the RC, a total of 669 genes were identified as being differentially upregulated, and 365 differentially downregulated. Real-time quantitative RT-PCR analysis was used to confirm upregulated genes in the RC. In addition, using the technique of laser microdissection (LMD) we localized upregulated gene expression to the lateral RC cells. Taken as a whole, transcription profile analyses revealed the upregulation in the maize RC of clusters of genes linked to major metabolic processes and pathways, including: (1) transport, both the export of carbohydrates and the uptake of nutrients; (2) sensing and responding to (often stressful) biotic and abiotic environmental stimuli; (3) integrating the responses of at least 3 major growth regulators (auxin, ethylene, jasmonic acid); (4) processing the large amount of carbohydrate transported into the RC. Although the profile data are derived using heterologous rice GeneChips, with about half of the total rice gene set, this study, nevertheless, provides a genomic scale characterization of the entire RC, and serves as a new platform from which to advance studies of the network of pathways operating in the maize RC.

Arabidopsis↗

PubMed2005

Effect of serum on the down-regulation of CHOP-10 during differentiation of 3T3-L1 preadipocytes.

Hormonal induction of growth-arrested 3T3-L1 preadipocytes in medium containing fetal bovine serum (FBS) triggers a signaling cascade that culminates in adipogenesis. The transcription factor, C/EBPbeta, is expressed early in this differentiation program, but lacks DNA-binding activity until much later as the preadipocytes traverse the G(1)-S checkpoint of mitotic clonal expansion. Dominant-negative CHOP-10 is initially expressed by growth-arrested preadipocytes and sequesters/inactivates C/EBPbeta by heterodimerization with its leucine zipper. After a lag period, CHOP-10 undergoes down-regulation releasing C/EBPbeta from inhibitory constraint allowing transactivation of the C/EBPalpha and PPARgamma genes, transcription factors required for terminal differentiation. We verify that following induction of differentiation in FBS-containing medium, CHOP-10 undergoes down-regulation and differentiation occurs normally. However, when differentiation is induced in calf serum-containing medium, CHOP-10 is not down-regulated resulting in delayed and incomplete differentiation. Under these conditions the expression of C/EBPalpha and PPARgamma and the accumulation of cytoplasmic triglyceride are attenuated. It appears that a factor(s) present in FBS is required to affect the down-regulation of CHOP-10 necessary for successful terminal differentiation.

3T3-L1 Cells↗

PubMed2005

Activation of the steroid and xenobiotic receptor (human pregnane X receptor) by nontaxane microtubule-stabilizing agents.

PURPOSE: Because induction of drug efflux transporters is one of the major underlying mechanisms of drug resistance in cancer chemotherapy, and human pregnane X receptor (hPXR) is one of the principal "xenobiotic" receptors whose activation induces transporter and drug-metabolizing enzyme gene transcription, it would be ideal to develop chemotherapy drugs that do not activate hPXR. This report describes studies undertaken to explore the characteristics of hPXR stimulation and mechanisms of drug-receptor interactions in vitro with new anti-tubulin drugs. EXPERIMENTAL DESIGN: In vitro transient transcription, glutathione S-transferase pull-down assays, and mammalian one-hybrid and two-hybrid systems were used to explore drug-receptor interactions. Loss of righting reflex was used to assess effects of drugs on PXR activity in vivo. RESULTS: The current study showed that paclitaxel, discodermolide, and an analogue of epothilone B, BMS-247550, induced CYP3A4 protein expression in HepG2 hepatoma cells. Transient transcription assays of a luciferase reporter in the presence and absence of a GAL4-steroid and xenobiotic receptor (SXR) plasmid in HepG2 cells showed that these drugs activate hPXR. This was not true for the inactive analogue of paclitaxel, baccatin III, or for an analogue of epothilone A, analogue 5, none of which stabilizes microtubules. To determine the mechanisms by which paclitaxel, discodermolide, and BMS-247550 activate hPXR, a mammalian two-hybrid assay was done using VP16SRC-1 (coactivator) and GAL4-SXR. SRC-1 preferentially augmented the effects of these drugs on hPXR. Expression of SMRT (corepressor) but not NCoR suppressed the drug-induced activation of SXR by approximately 50%, indicating a selectivity in corepressor interaction with hPXR. These drugs resulted in shortened duration of loss of righting reflex in vivo, indicating drug-induced activation of PXR in mice. CONCLUSION: These findings suggest that activation of hPXR with selective displacement of corepressors is an important mechanism by which microtubule-stabilizing drugs induce drug-metabolizing enzymes both in vitro and in vivo.

Alkanes↗

PubMed2005

Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and glycogen synthase kinase 3beta is required for adipogenesis.

CCAAT enhancer-binding protein (C/EBP)beta, C/EBPalpha, and peroxisome proliferator activated receptor (PPAR)gamma act in a cascade where C/EBPbeta activates expression of C/EBPalpha and PPARgamma, which then function as pleiotropic activators of genes that produce the adipocyte phenotype. When growth-arrested 3T3-L1 preadipocytes are induced to differentiate, C/EBPbeta is rapidly expressed but still lacks DNA-binding activity. After a long (14-hour) lag, glycogen synthase kinase 3beta enters the nucleus, which correlates with hyperphosphorylation of C/EBPbeta and acquisition of DNA-binding activity. Concurrently, 3T3-L1 preadipocytes synchronously enter S phase and undergo mitotic clonal expansion, a prerequisite for terminal differentiation. Ex vivo and in vitro experiments with C/EBPbeta show that phosphorylation of Thr-188 by mitogen-activating protein kinase "primes" C/EBPbeta for subsequent phosphorylation on Ser-184 and Thr-179 by glycogen synthase kinase 3beta, acquisition of DNA-binding function, and transactivation of the C/EBPalpha and PPARgamma genes. The delayed transactivation of the C/EBPalpha and PPARgamma genes by C/EBPbeta appears necessary to allow mitotic clonal expansion, which would otherwise be prevented, because C/EBPalpha and PPARgamma are antimitotic.

3T3-L1 Cells↗

PubMed2005

The Genomes of Oryza sativa: a history of duplications.

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.

Base Sequence↗

PubMed2005

Functional annotation and network reconstruction through cross-platform integration of microarray data.

The rapid accumulation of microarray data translates into a need for methods to effectively integrate data generated with different platforms. Here we introduce an approach, 2(nd)-order expression analysis, that addresses this challenge by first extracting expression patterns as meta-information from each data set (1(st)-order expression analysis) and then analyzing them across multiple data sets. Using yeast as a model system, we demonstrate two distinct advantages of our approach: we can identify genes of the same function yet without coexpression patterns and we can elucidate the cooperativities between transcription factors for regulatory network reconstruction by overcoming a key obstacle, namely the quantification of activities of transcription factors. Experiments reported in the literature and performed in our lab support a significant number of our predictions.

Algorithms↗

PubMed2005

[Study on differential display genes of tolerant-damage of MRC-5 induced by formaldehyde of low dose].

OBJECTIVE: To observe the differentially expressed genes of the human embryo lung fibroblast (MRC-5) induced by formaldehyde (FA) of low dose using fluoro DD-PCR. METHODS: The dose-effect relation of FA toxicity to MRC-5 was acquired, No observed damage effect or proliferation concentration was used as low dose, and obvious damage concentration was used as high dose. MRC-5 was treated with low and high dose, and treated with high dose after pretreated with low dose for some time. Then Fluoro differential display polymerase chain reaction (Fluoro DD-PCR) was used to search differentially expressed genes of the differently treated groups of FA. 61 differential display straps were acquired and 11 of them were reamplified, cloned, sequenced and blasted. RESULTS: According to the dose-effect relation of FA toxicity to MRC-5, 100 micromol/L was choosed as low dose and 10 mmol/L was choosed as high dose. Samples of differently treated groups were amplified by means of fluro-DD-PCR, 61 differentially expressed straps were acquired. 11 differential display straps have been cloned, sequenced and blasted. Two of them were known genes: one was highly homologous to nuclear factor of activated T-cells 5 (NFAT5) and the other was highly homologous to tetratricopeptide repeat domain 3(TPRD-3). Nine of them were new genes. CONCLUSION: It seemed that FA of low dose could promote MRC-5 proliferation and find 61 differentially expressed genes of differently treated groups, and the result of clone could provide scientific base for mechanism of FA toxicity research.

Cell Line↗

PubMed2005

[Adaptive response induced by low concentration of hydroquinone in human embryonic fibroblasts cells].

OBJECTIVE: To study the adaptive response induced by hydroquinone(HQ) on eukaryocyte and its possible mechanism. METHODS: After hydroquinone treatment, AlamarBlue reduce rate, LDH release rate were observed to determine the cell proliferation and death. Annexin V/propidium iodide (PI) staining was performed for each treatment to distinguish viable, early, and late apoptosis or dead cells. The total cellular proteins were separated using two- dimensional gel electrophoresis and visualized by sliver staining. Digital images were analyzed using ImageMaster 2D platinum 5.0 software. The differentially expressed protein spots were picked and digested in gel then identified by tandem mass spectrum. RESULTS: The results of AlamarBlue reduce rate, LDH leakage and Annexin V-FITC/PI staining showed that no effect on cell viability was observed at a concentration of 10 micromol/L HQ while 250 micromol/L HQ significantly decreased cell viability. Cells pretreated with 10 micromol/L HQ for 12h show increasing survival to the following expose to 250 micromol/L HQ. In control MRC-5 cells 1429 +/- 369 protein spots were detected and, 1453 +/- 307 in low HQ group, 1191 +/- 393 in high HQ group, and 1107 +/- 247 in adaptive group by two dimensional gel electrophoresis. Twenty-four protein spots showed significant change after HQ stimulation and 22 protein spots were identified by tandems mass spectra. These identified proteins involved in energy metabolism, translation and RNA processing, protein folding, redox regulation, cell structure and cell signaling. CONCLUSION: Adaptive response can be induced by low concentration of HQ on MRC-5 cells and cellular adaptation is a complex process involving in a modulation of diverse cellular functions.

Apoptosis↗

PubMed2004

A draft sequence for the genome of the domesticated silkworm (Bombyx mori).

We report a draft sequence for the genome of the domesticated silkworm (Bombyx mori), covering 90.9% of all known silkworm genes. Our estimated gene count is 18,510, which exceeds the 13,379 genes reported for Drosophila melanogaster. Comparative analyses to fruitfly, mosquito, spider, and butterfly reveal both similarities and differences in gene content.

Algorithms↗

PubMed2004

Clustering analysis of SAGE data using a Poisson approach.

Serial analysis of gene expression (SAGE) data have been poorly exploited by clustering analysis owing to the lack of appropriate statistical methods that consider their specific properties. We modeled SAGE data by Poisson statistics and developed two Poisson-based distances. Their application to simulated and experimental mouse retina data show that the Poisson-based distances are more appropriate and reliable for analyzing SAGE data compared to other commonly used distances or similarity measures such as Pearson correlation or Euclidean distance.

Animals↗

PubMed2004

Genomic analysis of mouse retinal development.

The vertebrate retina is comprised of seven major cell types that are generated in overlapping but well-defined intervals. To identify genes that might regulate retinal development, gene expression in the developing retina was profiled at multiple time points using serial analysis of gene expression (SAGE). The expression patterns of 1,051 genes that showed developmentally dynamic expression by SAGE were investigated using in situ hybridization. A molecular atlas of gene expression in the developing and mature retina was thereby constructed, along with a taxonomic classification of developmental gene expression patterns. Genes were identified that label both temporal and spatial subsets of mitotic progenitor cells. For each developing and mature major retinal cell type, genes selectively expressed in that cell type were identified. The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions. In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs") were found to be dynamically and specifically expressed in developing and mature retinal cell types. Finally, many photoreceptor-enriched genes that mapped to chromosomal intervals containing retinal disease genes were identified. These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

Animals↗

PubMed2004

Molecular characterization of the tumor microenvironment in breast cancer.

Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.

Biomarkers, Tumor↗

PubMed2004

Determination of local statistical significance of patterns in Markov sequences with application to promoter element identification.

High-level eukaryotic genomes present a particular challenge to the computational identification of transcription factor binding sites (TFBSs) because of their long noncoding regions and large numbers of repeat elements. This is evidenced by the noisy results generated by most current methods. In this paper, we present a p-value-based scoring scheme using probability generating functions to evaluate the statistical significance of potential TFBSs. Furthermore, we introduce the local genomic context into the model so that candidate sites are evaluated based both on their similarities to known binding sites and on their contrasts against their respective local genomic contexts. We demonstrate that our approach is advantageous in the prediction of myogenin and MEF2 binding sites in the human genome. We also apply LMM to large-scale human binding site sequences in situ and found that, compared to current popular methods, LMM analysis can reduce false positive errors by more than 50% without compromising sensitivity. This improvement will be of importance to any subsequent algorithm that aims to detect regulatory modules based on known PSSMs.

Algorithms↗

PubMed2004

[Protein changes in human embryonic lung fibroblasts after hydroquinone stimulation using proteomic technique].

OBJECTIVE: To explore the molecular mechanism of cell response induced by hydroquinone, we investigated the protein profile after treatment with hydroquinone in human embryonic lung fibroblasts. METHODS: After HQ treatment, cells were lysed in lysis solution, then the supernatant were collected and precipitated with acetone prior to protein concentration determination. The total cellular proteins were separated using two-dimensional gel electrophoresis and visualized by colloidal coomassie blue staining. Digital images were analyzed using Imagemaster 2.0 software. The differentially expressed protein spots were picked and digestion in gel then identified by peptide mass fingerprinting using MALDI-TOF. RESULTS: There were 15 protein spots changed after HQ stimulation. Among them 8 protein spots were identified by PMF including some oxidative stress and cytoskeleton related proteins. CONCLUSION: Protein profile was altered after HQ stimulation.

Cells, Cultured↗

PubMed2002

Distributional regimes for the number of k-word matches between two random sequences.

When comparing two sequences, a natural approach is to count the number of k-letter words the two sequences have in common. No positional information is used in the count, but it has the virtue that the comparison time is linear with sequence length. For this reason this statistic D(2) and certain transformations of D(2) are used for EST sequence database searches. In this paper we begin the rigorous study of the statistical distribution of D(2). Using an independence model of DNA sequences, we derive limiting distributions by means of the Stein and Chen-Stein methods and identify three asymptotic regimes, including compound Poisson and normal. The compound Poisson distribution arises when the word size k is large and word matches are rare. The normal distribution arises when the word size is small and matches are common. Explicit expressions for what is meant by large and small word sizes are given in the paper. However, when word size is small and the letters are uniformly distributed, the anticipated limiting normal distribution does not always occur. In this situation the uniform distribution provides the exception to other letter distributions. Therefore a naive, one distribution fits all, approach to D(2) statistics could easily create serious errors in estimating significance.

Computer Simulation↗

PubMedDate not supplied

Finding short DNA motifs using permuted Markov models.

Many short DNA motifs, such as transcription factor binding sites (TFBS) and splice sites, exhibit strong local as well as nonlocal dependence. We introduce permuted variable length Markov models (PVLMM) which could capture the potentially important dependencies among positions and apply them to the problem of detecting splice and TFB sites. They have been satisfactory from the viewpoint of prediction performance and also give ready biological interpretations of the sequence dependence observed. The issue of model selection is also studied.

Algorithms↗