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Biomedical subjects

Hongyu Li

Publications and source records attributed to Hongyu Li.

14 recordsLinked to original sources
PubMed2026

Microglial PICALM: A novel genetic driver and therapeutic target in vascular dementia.

BACKGROUND: Vascular dementia (VaD) lacks well-defined genetic mechanisms. Cell-type-specific effects of GWAS loci remain unexplored. METHODS: We integrated single&#x2011;cell eQTL data (183 donors, eight cell types) with VaD GWAS (3624 cases, 475,484 controls) using Mendelian randomization and Bayesian colocalization, replicated in an independent cohort (2074 cases, 456,366 controls). Subtype, snRNA&#x2011;seq, cell&#x2011;cell communication, PheWAS, expression profiling, and drug prediction with BBB permeability assessment were performed. RESULTS: Microglial PICALM was the only robustly replicated signal (OR = 0.8334, p = 5.3 &#xd7; 10&#x207b;&#x2074;; colocalization PP.H4 > 0.75). The effect was strongest in multiple infarctions dementia (OR = 0.7746). Exploratory snRNA-seq analysis (4 VaD vs. 4 controls; GSE282111) provided supporting evidence for microglial PICALM enrichment and downregulation (p < 0.001). PICALM&#x2011;high microglia showed enhanced neurovascular&#x2011; and phagocytosis&#x2011;related communication (e.g., SPP1, GAS6, GRN). PheWAS revealed no pleiotropy. In silico drug repurposing prioritised three FDA-approved BBB-penetrant compounds (disopyramide, benzocaine, amantadine) as candidates warranting further mechanistic validation. CONCLUSIONS: Microglial PICALM is identified as a likely genetic determinant of VaD, especially in the multiple infarctions subtype. Upregulating PICALM may be associated with a neuroprotective microglial phenotype, highlighting PICALM as a candidate therapeutic target warranting further experimental validation.

Humans↗
PubMed2006

Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma.

Epigenetic mechanisms involving DNA methylation and chromatin remodeling are important in silencing tumor suppressor genes (TSG) in various malignancies, including renal cell carcinoma (RCC). DLC1 (deleted in liver cancer 1)/ARHGAP7 is a recently identified 8p22 candidate TSG. Frequent methylation of the DLC1 promoter with resultant gene silencing has been reported in several tumors, but not in RCC yet. We examined DLC1 promoter methylation in 34 primary RCCs and the corresponding non-malignant tissues, and the correlation of DLC1 methylation with the clinicopathological characteristics of RCC patients. Although DLC1 methylation and downregulation were only detected in one of seven RCC cell lines using methylation-specific PCR (MSP) and semi-quantitative reverse-transcription PCR, we found that the DLC1 promoter was methylated in 35% (12/34) of primary RCC tumors, which was further confirmed by direct sequencing of MSP products and high-resolution bisulfite genomic sequencing. In contrast, only one of the 34 (3%) non-malignant renal tissues had weak methylation. Aberrant DLC1 methylation appeared to be a relatively early event during renal tumorigenesis since 33% of the RCC tumors with pT1 (TNM staging) showed methylation, which is similar to other late stage tumors. Thus, our results demonstrated that DLC1 methylation occurs in a subset of RCC tumors and may play a role in renal carcinogenesis.

Adult↗
PubMed2006

Expression of Pin1 and Ki67 in cervical cancer and their significance.

In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P < 0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P < 0.05). No significant difference in the Pin1 expression was found between disease stages (FIGO), pathological grades or pelvic lymph node metastasis status (P > 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.

Biomarkers, Tumor↗
PubMed2006

Construction and characterization of a rock-cluster-based EST analysis pipeline.

Open access to vast amount of expression sequence tags (ESTs) data in the public databases has provided a powerful platform for gene identification, gene expression studies and comparative/functional genomic studies. To facilitate management of large-scale EST data, high performance cluster and analysis softwares, especially parallel softwares, are fundamentally essential. We reported herein a convenient approach to construct a high performance computating (HPC) cluster based on popular Rocks and a perl-scripted analysis pipeline for EST pre-processing, clustering, assembling and annotation and any other desired analysis modules through parallel computing. We tested the system using different datasets on increasing nodes. Our present results showed that the cluster and pipeline accelerate the EST analysis without artificial interference.

Cluster Analysis↗
PubMed2006

Pin1 contributes to cervical tumorigenesis by regulating cyclin D1 expression.

The prolyl isomerase Pin1, which specifically catalyzes conformational changes in certain proline-directed phosphorylation sites, is thought to be a critical catalyst for multiple oncogenic pathways. However, little is known about the role of Pin1 in human cervical cancer. Our previous study showed that Pin1 was overexpressed in cervical cancer tissues as well as cell lines. In this study, whether Pin1 is involved in cervical oncogenesis by regulating cyclin D1 was explored and the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in cervical cancer was investigated. A Pin1-directed shRNA and a sense Pin1 plasmid were constructed, and then the effects of the shRNA and the sense plasmid on HeLa cells were evaluated. The results showed that Pin1 directly regulated cyclin D1 levels. In addition, silencing Pin1 with RNAi significantly reduced cancer cell proliferation, colony formation, and strongly enhanced the apoptosis of HeLa cells. It is suggested that Pin1 may contribute to cervical tumorigenesis by regulating cyclin D1 expression and Pin1 may serve as a promising molecular target for diagnostics and therapeutics in cervical cancer.

Apoptosis↗
PubMed2004

Determination of CFTR chloride channel activity and pharmacology using radiotracer flux methods.

Flux studies using either radioisotopes or ion-selective electrodes are a convenient method to assay the function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Here, we described three different protocols to study the properties, regulation and pharmacology of the CFTR Cl- channel in populations of cells and artificial vesicles. These techniques are widely used to evaluate the function of wild-type and mutant CFTR prior to detailed analyses using the patch-clamp technique. Moreover, they have proved especially valuable in the search for new drugs to treat cystic fibrosis.

Cell Culture Techniques↗
PubMed2004

Transepithelial electrical measurements with the Ussing chamber.

The Ussing chamber technique is a simple, but powerful technique to investigate ion transport. Originally designed to study vectorial ion transport through the frog skin, it has revolutionized our knowledge about how eletrolytes permeate epithelia. Here we discuss the physiological principles that underlie the technique and protocols to investigate the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in transepithelial ion transport.

Cell Membrane↗
PubMed2004

Strategies to investigate the mechanism of action of CFTR modulators.

The malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is associated with a wide spectrum of disease. In the search for modulators of CFTR, pharmaceutical agents have been identified that (i) act indirectly by regulating the protein kinases and phosphatases, which control CFTR, and (ii) interact directly with CFTR. Some agents modulate CFTR by altering the function of the nucleotide-binding domains (NBDs) that control channel gating, whereas others inhibit CFTR by preventing Cl- flow through the channel pore. Knowledge of CFTR modulators might lead to new understanding of the CFTR Cl- channel, its physiological role and malfunction in disease.

Chlorides↗
PubMed2004

The patch-clamp and planar lipid bilayer techniques: powerful and versatile tools to investigate the CFTR Cl- channel.

Using the patch-clamp (PC) and planar lipid bilayer (PLB) techniques the molecular behaviour of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel can be visualised in real-time. The PC technique is a highly powerful and versatile method to investigate CFTR's mechanism of action, interaction with other proteins and physiological role. Using the PLB technique, the structure and function of CFTR can be investigated free from the influence of other proteins. Here we discuss how these techniques are employed to investigate the CFTR Cl- channel with special emphasis on its permeation, conduction and gating properties.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2004

The relationship between cell proliferation, Cl- secretion, and renal cyst growth: a study using CFTR inhibitors.

BACKGROUND: In autosomal-dominant polycystic kidney disease (ADPKD), cAMP-stimulated cell proliferation and Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel drive the enlargement of fluid-filled epithelial cysts. To investigate how CFTR blockers inhibit cyst growth, we studied cAMP-dependent Cl- secretion, cell proliferation, and cyst growth using type I Madin Darby canine kidney (MDCK) cells as a model of renal cyst development and growth. METHODS: We grew MDCK cysts in collagen gels in the presence of the cAMP agonist forskolin, measured Cl- secretion with the Ussing chamber technique, and assayed cell proliferation using nonpolarized and polarized MDCK cells. To inhibit CFTR, we used glibenclamide, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), genistein, and the specific CFTR inhibitor CFTRinh-172. As controls, we tested the effects of blockers of other types of apical membrane Cl- channels and inhibitors of basolateral membrane ion channels and transporters. RESULTS: In the absence of inhibitors of transepithelial ion transport, forskolin stimulated dramatic cyst growth. CFTR blockers and inhibitors of basolateral membrane ion channels and transporters retarded cyst growth. In contrast, blockers of other types of apical membrane Cl- channels, which were without effect on CFTR, failed to inhibit cyst growth. Inhibition of cyst growth by CFTR blockers was correlated with inhibition of cAMP-stimulated Cl- current (correlation coefficient = 0.81; P < 0.05), but not cell proliferation (correlation coefficient = 0.50; P > 0.05). CONCLUSION: Our data suggest that CFTR blockers might retard cyst growth predominantly by inhibiting fluid accumulation within the cyst lumen.

Animals↗
PubMed2004

[Effect of insect pest on activated oxygen metabolism in lanceolate leaves of Populus euphratica under different water condition].

This paper studied the effect of insect pest on the activities of protective enzymes SOD and CAT and the contents of H2O2 and O2*- in lanceolate leaves of Populus euphratica under different soil water conditions. The results showed that soil water deficiency did not increase SOD and CAT activities and H2O2 and O2*- contents in lanceolate leaves, but under this condition, insect pest increased them. When soil water was abundance, insect pest couldn't increase the activities of SOD and CAT and the contents of H2O2 and O2*- in lanceolate leaves. It's concluded that insect pest had an important role in death of Populus euphratica under soil water deficiency.

Animals↗
PubMed2003

[Studies on chemical constituents from Phyllostachys pubescens].

OBJECTIVE: To study the chemical constituents from Phyllostachys pubescens. METHODS: A extract of P. pubescens was prepared by decocting with boiling water, chromatographed on macroporus resin column and eluted by ethanol. The eluant was separated on silica gel column by eluting with various proportions of chloroform-methanol-water. UV, MS, 1H NMR and 13C NMR were used to elucidate these chemical constituents structure. RESULT: Two compounds were isolated as vitexin (I) and orientin (II). CONCLUSION: Two compounds were isolated from this genus for the first time.

Apigenin↗
PubMedDate not supplied

Segmentation of discrete vector fields.

In this paper, we propose an approach for 2D discrete vector field segmentation based on the Green function and normalized cut. The method is inspired by discrete Hodge Decomposition such that a discrete vector field can be broken down into three simpler components, namely, curl-free, divergence-free, and harmonic components. We show that the Green Function Method (GFM) can be used to approximate the curl-free and the divergence-free components to achieve our goal of the vector field segmentation. The final segmentation curves that represent the boundaries of the influence region of singularities are obtained from the optimal vector field segmentations. These curves are composed of piecewise smooth contours or streamlines. Our method is applicable to both linear and nonlinear discrete vector fields. Experiments show that the segmentations obtained using our approach essentially agree with human perceptual judgement.

Algorithms↗