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Biomedical subjects

Qing Lu

Publications and source records attributed to Qing Lu.

At least 19 recordsLinked to original sources
PubMed2026

A Phosphoproteomic Platform Identifies Erythrocyte Membrane Protein Band 4.1-Like 3-Mediated Lipid Droplet Remodeling Linked to Liver Cancer Invasion and Migration.

Aberrant lipid metabolism is a hallmark of hepatocellular carcinoma (HCC), yet the regulatory mechanisms governing lipid droplet (LD) dynamics and their contribution to tumor progression remain poorly understood. Here, we developed an ultrasensitive phosphoproteomic platform using high-affinity HPDA@Ti4+ nanospheres to map LD-associated phosphorylation events across six HCC cell lines. By correlating phosphoproteomic signatures with LD morphology, we identified distinct regulatory signatures associated with LD size and abundance. Functional perturbation screens identified two distinct phosphoprotein modules controlling LD size: silencing SH3KBP1, SLK, EHD2, EPB41L3, and NEXN reduced LD size in Huh1 cells, whereas silencing CPD, BET1, UFL1, RRP1B, OGFR, and CD2BP2 enlarged LDs in Huh7 cells. Notably, we identified EPB41L3 as a critical metabolic-metastatic link; its loss decreased LD size and accelerated HCC migration and invasion, correlating with poor clinical prognosis. Crucially, we identified five key phosphorylation sites on EPB41L3 essential for its function; substituting these with alanine completely abolished its regulatory control over both LD size and HCC metastatic potential. Together, these findings delineate a phosphorylation-based regulatory network controlling the LD architecture and metastatic potential in HCC. Our study not only identifies potential therapeutic targets but also establishes a generalizable phosphoproteomic framework for interrogating lipid signaling in cancer metabolism.

Humans↗
PubMed2025

Functional analysis of a GWAS pleiotropic hotspot suggests an auxin biosynthesis gene (AhPDS1), regulating pod development in peanut (Arachis hypogaea L.).

Peanut productivity and quality improvement rely on understanding the genetic factors influencing pod and seed size. This study aims to identify genetic factors and regulatory mechanisms influencing pod and seed size in peanuts. Herein, a genome-wide association study (GWAS) was conducted using 390 accessions from 15 peanut growing regions to analyze pod and seed traits across multiple planting seasons. A significant phenotypic variation was observed, with broad-sense heritability ranging from 53.6 to 85.4%. Strong correlations between pod and seed traits further suggest potential for co-selection in breeding efforts. A pleiotropic hotspot on chromosome B06 was strongly associated with six pod and seed traits. A peanut pod size regulator AhPDS1 (PODSIZE-1, Ahy_B06g085516) homolog of Arabidopsis thaliana YUCCA4 (AtYUC4, AT5G11320), involved in auxin biosynthesis, was selected as a candidate regulating pod and seed size. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) confirmed higher AhPDS1 expression in large pod as compared with the small pod genotypes. Subcellular localization showed AhPDS1 to be predominantly cytoplasmic, and GUS reporter assays indicated widespread expression in roots, stems, leaves, flowers, and pods, suggesting a broad functional role. Further overexpression of AhPDS1 in Arabidopsis and rice enhanced pod, seed, and grain sizes via the indole-3-pyruvic acid pathway in transgene lines. These findings highlight AhPDS1 as a potential target for peanut molecular breeding, offering opportunities to enhance pod size via auxin biosynthesis and support sustainable crop improvement.

Arachis↗
PubMed2006

Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes.

Pre-eclampsia (PE) affects 5-7% of pregnancies in the US, and is a leading cause of maternal death and perinatal morbidity and mortality worldwide. To identify genes with a role in PE, we conducted a large-scale association study evaluating 775 SNPs in 190 candidate genes selected for a potential role in obstetrical complications. SNP discovery was performed by DNA sequencing, and genotyping was carried out in a high-throughput facility using the MassARRAY(TM) System. Women with PE (n = 394) and their offspring (n = 324) were compared with control women (n = 602) and their offspring (n = 631) from the same hospital-based population. Haplotypes were estimated for each gene using the EM algorithm, and empirical p values were obtained for a logistic regression-based score test, adjusted for significant covariates. An interaction model between maternal and offspring genotypes was also evaluated. The most significant findings for association with PE were COL1A1 (p = 0.0011) and IL1A (p = 0.0014) for the maternal genotype, and PLAUR (p = 0.0008) for the offspring genotype. Common candidate genes for PE, including MTHFR and NOS3, were not significantly associated with PE. For the interaction model, SNPs within IGF1 (p = 0.0035) and IL4R (p = 0.0036) gave the most significant results. This study is one of the most comprehensive genetic association studies of PE to date, including an evaluation of offspring genotypes that have rarely been considered in previous studies. Although we did not identify statistically significant evidence of association for any of the candidate loci evaluated here after adjusting for multiple testing using the false discovery rate, additional compelling evidence exists, including multiple SNPs with nominally significant p values in COL1A1 and the IL1A region, and previous reports of association for IL1A, to support continued interest in these genes as candidates for PE. Identification of the genetic regulators of PE may have broader implications, since women with PE are at increased risk of death from cardiovascular diseases later in life.

Adult↗
PubMed2006

RACK1 is a BKCa channel binding protein.

The large conductance calcium-activated potassium channel, or BK(Ca) channel, plays an important feedback role in a variety of physiological processes, including neurotransmitter release and smooth muscle contraction. Some reports have suggested that this channel forms a stable complex with regulators of its function, including several kinases and phosphatases. To further define such signaling complexes, we used the yeast two-hybrid system to screen a human aorta cDNA library for proteins that bind to the BK(Ca) channel's intracellular, COOH-terminal "tail". One of the interactors we identified is the protein receptor for activated C kinase 1 (RACK1). RACK1 is a member of the WD40 protein family, which also includes the G protein beta-subunits. Consistent with an important role in BK(Ca)-channel regulation, RACK1 has been shown to be a scaffolding protein that interacts with a wide variety of signaling molecules, including cSRC and PKC. We have confirmed the interaction between RACK1 and the BK(Ca) channel biochemically with GST pull-down and coimmunoprecipitation experiments. We have observed some co-localization of RACK1 with the BK(Ca) channel in vascular smooth muscle cells with immunocytochemical experiments, and we have found that RACK1 has effects on the BK(Ca) channel's biophysical properties. Thus RACK1 binds to the BK(Ca) channel and it may form part of a BK(Ca)-channel regulatory complex in vascular smooth muscle.

Amino Acid Sequence↗
PubMed2006

Pharmacology and signaling properties of epidermal growth factor receptor isoforms studied by bioluminescence resonance energy transfer.

We have developed a new assay for measuring epidermal growth factor receptor (EGFR) activation using the bioluminescence resonance energy transfer (BRET) technology, which directly measures the recruitment of signaling proteins to activated EGFR. Our results demonstrate that EGFR BRET assays precisely measure the pharmacology and signaling properties of EGFR expressed in human embryonic kidney 293T cells. EGFR BRET assays are highly sensitive to known EGFR ligands [pEC50 of epidermal growth factor (EGF)=10.1+/-0.09], consistent with previous pharmacological methods for measuring EGFR activation. We applied EGFR BRET assays to study the characteristics of somatic EGFR mutations that were recently identified in lung cancer. In agreement with recent reports, we detected constitutively active mutant EGFR isoforms, which predominantly signal through the phosphatidylinositol-3-kinase/Akt pathway. The EGFR inhibitors Iressa or Tarceva are severalfold more potent in inhibiting constitutive activity of mutant EGFR isoforms compared with wild-type EGFR. Notable, our results reveal that most of the mutant EGFR isoforms tested were significantly impaired in their response to EGF. The highest level of constitutive activity and nearly complete loss of epidermal growth factor responsiveness was detected in isoforms that carry the activating mutation L858R and the secondary resistance mutation T790M. In summary, our study reveals that somatic mutations in EGFR quantitatively differ in pharmacology and signaling properties, which suggest the possibility of differential clinical responsiveness to treatment with EGFR inhibitors. Furthermore, we demonstrate that the EGFR BRET assays are a useful tool to study the pharmacology of ligand-induced interaction between EGFR and signaling pathway-specifying adapter proteins.

Cell Line↗
PubMed2006

[Hepatic safety of itraconazole intravenous solution in treatment of invasive fungal infection].

OBJECTIVE: To investigate the hepatic safety of itraconazole intravenous solution in the treatment of invasive fungal infection. METHODS: Forty-nine patients with invasive fungal infection, such as pneumonia, meningitis, endocarditis, and blood stream infection, caused by Aspergillus spp. Cryptococcus neoformans, Candida spp. Penicillium marneffei, and Prototheca wickerhamii, 50 of which had underlying diseases, including hepatic diseases, such as hepatitis, cirrhosis, fatty liver etc. were treated with intravenous itraconazole for 12.6 days (2 - 42 days). Liver function test was conducted before and after the treatment. The relationship between liver adverse reaction and itraconazole treatment was evaluated. RESULTS: Liver function test was abnormal in 20 patients. The patients with liver enzyme abnormalities before itraconazole treatment were easier to suffer from hepatic damage during itraconazole treatment (chi(2) = 11.54, P = 0.001). However, only in 2 patients with mild liver function test abnormality the liver adverse reaction could be associated with itraconazole treatment. CONCLUSION: Itraconazole treatment for invasive fungal infection is rather safe, even in the patients with underlying hepatic diseases. Liver function test is recommended for all patients suggestive of liver dysfunction and protective therapy for liver is needed.

Adolescent↗
PubMed2006

Hydrogen sulphide regulates calcium homeostasis in microglial cells.

Hydrogen sulphide (H2S), which is produced endogenously from L-cysteine in mammalian tissues, has been suggested to function as a neuromodulator in the brain. However, the role of H2S in microglial cells is unclear. In this study, the effect of exogenous and endogenous H2S on intracellular calcium homeostasis was investigated in primary cultured microglial cells. Sodium hydrosulphide (NaHS), a H2S donor, caused a concentration-dependent (0.1-0.5 mM) increase in intracellular calcium concentration ([Ca2+]i). This effect was significantly attenuated in the presence of a calcium-free extracellular solution, Gd3+ (100 microM), a nonselective Ca2+ channel blocker, or thapsigargin (2 microM), an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase. These observations suggest that the increase in [Ca2+]i in response to H2S involves both calcium influx across the plasma membrane and calcium release from intracellular stores. The H2S-induced calcium elevation is partly attenuated by H-89, a selective cAMP-dependent protein kinase (PKA) inhibitor, but not by U73122, a phospholipase C (PLC) inhibitor, and chelerythrine, a selective protein kinase C (PKC) inhibitor, suggesting the involvement of cAMP/PKA, but not PLC/PKC/phosphoinositol-3,4,5-inositol (IP3) pathway. Using RT-PCR, only cystathionine gamma-lyase (CSE), a H2S producing enzyme, was detected in primary cultures of microglia. Lowering endogenous H2S level with, D,L-propargylglycine and beta-cyano-L-alanine, two CSE inhibitors, significantly decreased [Ca2+]i, suggesting that endogenous H2S may have a positive tonic influence on [Ca2+]i homeostasis. These findings support the possibility that H2S may serve as a neuromodulator to facilitate signaling between neurons and microglial cells.

Animals↗
PubMed2006

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study.

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Aortic Aneurysm, Abdominal↗
PubMed2006

Modeling extent and distribution of zygotic disequilibrium: implications for a multigenerational canine pedigree.

Unlike gametic linkage disequilibrium defined for a random-mating population, zygotic disequilibrium describes the nonrandom association between different loci in a nonequilibrium population that deviates from Hardy-Weinberg equilibrium. Zygotic disequilibrium specifies five different types of disequilibria simultaneously that are (1) Hardy-Weinberg disequilibria at each locus, (2) gametic disequilibrium (including two alleles in the same gamete, each from a different locus), (3) nongametic disequilibrium (including two alleles in different gametes, each from a different locus), (4) trigenic disequilibrium (including a zygote at one locus and an allele at the other), and (5) quadrigenic disequilibrium (including two zygotes each from a different locus). However, because of the uncertainty on the phase of the double heterozygote, gametic and nongametic disequilibria need to be combined into a composite digenic disequilibrium and further define a composite quadrigenic disequilibrium together with the quadrigenic disequilibrium. To investigate the extent and distribution of zygotic disequilibrium across the canine genome, a total of 148 dogs were genotyped at 247 microsatellite markers located on 39 pairs of chromosomes for an outbred multigenerational pedigree, initiated with a limited number of unrelated founders. A major portion of zygotic disequilibrium was contributed by the composite digenic and quadrigenic disequilibrium whose values and numbers of significant marker pairs are both greater than those of trigenic disequilibrium. All types of disequilibrium are extensive in the canine genome, although their values tend to decrease with extended map distances, but with a greater slope for trigenic disequilibrium than for the other types of disequilibrium. Considerable variation in the pattern of disequilibrium reduction was observed among different chromosomes. The results from this study provide scientific guidance about the determination of the number of markers used for whole-genome association studies.

Animals↗
PubMed2006

The affected-/discordant-sib-pair design can guarantee validity of multipoint model-free linkage analysis of incomplete pedigrees when there is marker-marker disequilibrium.

Genomewide linkage studies are tending toward the use of single-nucleotide polymorphisms (SNPs) as the markers of choice. However, linkage disequilibrium (LD) between tightly linked SNPs violates the fundamental assumption of linkage equilibrium (LE) between markers that underlies most multipoint calculation algorithms currently available, and this leads to inflated affected-relative-pair allele-sharing statistics when founders' multilocus genotypes are unknown. In this study, we investigate the impact that the degree of LD, marker allele frequency, and association type have on estimating the probabilities of sharing alleles identical by descent in multipoint calculations and hence on type I error rates of different sib-pair linkage approaches that assume LE. We show that marker-marker LD does not inflate type I error rates of affected sib pair (ASP) statistics in the whole parameter space, and that, in any case, discordant sib pairs (DSPs) can be used to control for marker-marker LD in ASPs. We advocate the ASP/DSP design with appropriate sib-pair statistics that test the difference in allele sharing between ASPs and DSPs.

Chromosome Mapping↗
PubMed2006

Transforming growth factor-beta1-induced endothelial barrier dysfunction involves Smad2-dependent p38 activation and subsequent RhoA activation.

Lung edema due to increased vascular permeability is a hallmark of acute lung injury and acute respiratory distress syndrome. Both p38 and RhoA signaling events are involved in transforming growth factor (TGF)-beta1-increased endothelial permeability; however, the mechanism by which these pathways cooperate is not clear. In this study, we hypothesized that TGF-beta1-induced changes in endothelial monolayer permeability and in p38 and RhoA activation are dependent on Smad2 signaling. We assessed the role of Smad2 in p38 activation and the role of p38 in RhoA activation by TGF-beta1. We found that TGF-beta1 caused Smad2 phosphorylation between 0.5 and 1 h of exposure in endothelial cells. Knockdown of Smad2 protein prevented TGF-beta1-induced p38 activation and endothelial barrier dysfunction. Furthermore, TGF-beta1-enhanced RhoA activation was dependent on p38 activation. Inhibition of the RhoA-Rho kinase signaling pathway blunted TGF-beta1-induced adherens junction disruption and focal adhesion complex formation. In addition, depletion of heat shock protein 27, a downstream signaling molecule of p38, did not prevent TGF-beta1-induced endothelial barrier dysfunction. Finally, inhibition of de novo protein expression blunted TGF-beta1-induced RhoA activation and endothelial barrier dysfunction. Our data indicate that TGF-beta1 induces endothelial barrier dysfunction involving Smad2-dependent p38 activation, resulting in RhoA activation by possible transcriptional regulation.

Animals↗
PubMed2006

Direct electrochemistry of hemoglobin in PHEA and its catalysis to H2O2.

Hemoglobin (Hb) was immobilized on glassy carbon (GC) electrode by a kind of synthetic water-soluble polymer, poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA). A pair of well-defined and quasi-reversible cyclic voltammetric peaks was achieved, which reflected the direct electron-transfer of the Fe(III)/Fe(II) couple of Hb. The formal potential (E degrees'), the apparent coverage (Gamma(*)) and the electron-transfer rate constant (k(s)) were calculated by integrating cyclic voltammograms experimental data. Scanning electron microscopy (SEM) demonstrated the morphology of Hb-PHEA film very different from the Hb and PHEA films. Ultraviolet visible (UV-vis) spectroscopy showed Hb in PHEA film remained its secondary structure similar to the native state. In respect that the immobilized protein remained its biocatalytic activity to the reduction of hydrogen peroxide (H(2)O(2)), a kind of mediator-free biosensor for H(2)O(2) could be developed. The apparent Michaelis-Menten constant (K(m)(app)) was estimated to be 18.05 microM. The biosensor exhibited rapid electrochemical response and good stability. Furthermore, uric acid (UA), ascorbic acid (AA) and dopamine (DA) had little interferences with the amperometric signal of H(2)O(2), which provide the perspective of this H(2)O(2) sensor to be used in biological environments.

Biosensing Techniques↗
PubMed2006

Model for mapping imprinted quantitative trait loci in an inbred F2 design.

The role of imprinting in shaping development has been ubiquitously observed in plants, animals, and humans. However, a statistical method that can detect and estimate the effects of imprinted quantitative trait loci (iQTL) over the genome has not been extensively developed. In this article, we propose a maximum likelihood approach for testing and estimating the imprinted effects of iQTL that contribute to variation in a quantitative trait. This approach, implemented with the EM algorithm, allows for a genome-wide scan for the existence of iQTL. This approach was used to reanalyze published data in an F(2) family derived from the LG/S and SM/S mouse strains. Several iQTL that regulate the growth of body weight by expressing paternally inherited alleles were identified. Our approach provides a standard procedure for testing the statistical significance of iQTL involved in the genetic control of complex traits.

Algorithms↗
PubMed2006

Real-time three-dimensional color Doppler flow imaging: an improved technique for quantitative analysis of aortic regurgitation.

The recently introduced real-time three-dimensional color Doppler flow imaging (RT-3D CDFI) technique provides a quick and accurate calculation of regurgitant jet volume (RJV) and fraction. In order to evaluate RT-3D CDFI in the noninvasive assessment of aortic RJV and regurgitant jet fraction (RJF) in patients with isolated aortic regurgitation, real-time three-dimensional echocardiographic studies were performed on 23 patients with isolated aortic regurgitation to obtain LV end-diastolic volumes (LVEDV), end-systolic volumes (LVESV) and RJV, and then RJF could be calculated. The regurgitant volume (RV) and regurgitant fraction (RF) calculated by two-dimensional pulsed Doppler (2D-PD) method served as reference values. The results showed that aortic RJV measured by the RT-3D CDFI method showed a good correlation with the 2D-PD measurements (r = 0.93, Y = 0.89X + 3.9, SEE = 8.6 mL, P < 0.001); the mean (SD) difference between the two methods was--1.5 (9.8) mL. % RJF estimated by the RT-3D CDFI method was also correlated well with the values obtained by the 2D-PD method (r = 0.88, Y = 0.71X + 14.8, SEE = 6.4%, P < 0.001); the mean (SD) difference between the two methods was--1.2 (7.9) %. It was suggested that the newly developed RT-3D CDFI technique was feasible in the majority of patients. In patients with eccentric aortic regurgitation, this new modality provides additional information to that obtained from the two-dimensional examination, which overcomes the inherent limitations of two-dimensional echocardiography by depicting the full extent of the jet trajectory. In addition, the RT-3D CDFI method is quick and accurate in calculating RJV and RJF.

Adolescent↗
PubMed2006

Real-time three-dimensional echocardiography in assessment of congenital double orifice mitral valve.

The application of real-time three-dimensional echocardiography (RT 3DE) in the diagnosis of double orifice mitral valve (DOMV) was explored. Five cases of DOMV were examined by using 2-dimensional echocardiography (2DE) and RT 3DE. The spatial morphology of malformed mitral valve and its change in hemodynamics were observed. DOMV associated with partial atrioventricular septal defect was found in 3 cases (in which 2 cases had cleft mitral valve) and isolated DOMV in 2 cases; and moderate to severe mitral regurgitation was detected in 3 cases, and mild mitral regurgitation in 1, and no regurgitation in 1 case; 1 case had complicated rhumatic heart disease. Three cases were preoperatively discovered by 2DE, while 2 missed (1 case was discovered postoperatively). Four cases were diagnosed by RT 3DE preoperatively, and 1 case was diagnosed postoperatively (not examined by RT 3DE preoperatively). It was suggested that RT 3DE is a reliable technique in the diagnosis of DOMV; it permitted comprehensive and noninvasive assessment of mitral valve and may supplement 2D TTE in the assessment of DOMV.

Abnormalities, Multiple↗
PubMed2006

HLA-DQA is associated with abdominal aortic aneurysms in the Belgian population.

Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with human leukocyte antigen (HLA) polymorphisms (HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles) in 387 AAA cases and 426 controls. We observed an association with the HLA-DQA1 locus among Belgian males, and found a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases and controls. In conclusion, this study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Alleles↗
PubMed2006

Assessment of atrial septal defect area changes during cardiac cycle by live three-dimensional echocardiography.

OBJECTIVES: To investigate the accuracy of measurement of the atrial septal defect (ASD)area and dynamic change by live three-dimensional echocardiography (L3DE). METHODS: L3DE was performed in patients with ASD using a three-dimensional workstation to obtain the en face view of the ASD and measure its area at the peak of P-wave, the peak of R-wave, the initial and the destination point of T-wave, and the period of P-T. Parameters derived from L3DE were compared with intraoperative measurements. RESULTS: The ASD area changed significantly during cardiac cycles (mean change 46.1%, p < 0.0001; range 15.2-72.5%), with the maximal area at endsystole and the minimal area at enddiastole. There was excellent correlation between L3DE and intraoperative measurements for the area of ASD at the peak of P-wave (r = 0.92). There were good correlations between the two methods during the other phases of cardiac cycle (r = 0.81-0.86). CONCLUSIONS: L3DE provides accurate and feasible measurements of the ASD area. Investigation of the dynamic changes during the cardiac cycle may lead to an improved understanding of the hemodynamics of ASD.

Adolescent↗