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Biomedical subjects

Wei Hou

Publications and source records attributed to Wei Hou.

At least 19 recordsLinked to original sources
PubMed2026

SCAN: A sample-to-answer cross-priming isothermal assay for on-site virus detection with RT-qPCR sensitivity and genomically similar virus differentiation specificity.

Genomically similar viruses often differ in pathogenicity and host tropism due to specific mutations, and failure to distinguish them risks misdiagnosis and ineffective control. Molecular methods can differentiate such viruses but require laboratory settings and skilled personnel, while field-deployable immunological methods suffer from cross-reactivity. To address this challenge, we developed SCAN (Sample-to-answer Cross-priming isothermal amplification Assay with Nucleic acid strip), a general framework for on-site detection of genomically similar viruses. Comparative bioinformatics of isolation and sequencing data identifies key conserved differential determinants for primer design, ensuring specificity and reducing non-specific amplification. A one-tube cross-priming isothermal amplification (CPA) enables rapid target amplification without thermal cycling, and the products are visually detected on a nucleic acid strip. All steps are integrated into a handheld, lightweight device (9.9&#x202f;&#xd7;&#x202f;4.4&#x202f;&#xd7;&#x202f;3.3&#x202f;cm, <200&#x202f;g) that also prevents aerosol contamination. Using transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV), the latter a natural mutant of TGEV, as a model, SCAN achieves a detection limit of 102 copies/&#x3bc;L with sensitivity comparable to RT-qPCR and supports sample-to-answer testing within 80&#x202f;min and simple operations. With verified high sensitivity, specificity, and accuracy, as well as field usability, SCAN provides a generalizable route for developing point-of-care tests (PoCT) that require precise field differentiation of closely related pathogens.

Cross-priming isothermal amplification↗
PubMed2026

CRISPR/Cas9-Mediated Generation and Characterization of an Ent2*/CyO Drosophila melanogaster Strain.

In this study, a CRISPR/Cas9-based genome-editing approach was used to introduce mutations in the equilibrative nucleoside transporter 2 (Ent2) gene in Drosophila melanogaster. Guide RNAs targeting the coding region of Ent2 were designed and co-injected with Cas9 mRNA into w1118 embryos. Mutant alleles were identified by Sanger sequencing and maintained as a stable Ent2*/CyO heterozygous line using a balancer chromosome. Subsequently, we evaluated body weight, climbing ability, survival rate, and the activities of superoxide dismutase (SOD) and catalase (CAT) in fruit flies at 22 &#xb0;C and 25 &#xb0;C, respectively. The results indicate that at both 22 &#xb0;C and 25 &#xb0;C, the body length and weight of Ent2*/CyO fruit flies were significantly reduced compared to the w1118, and their development was delayed. At 22 &#xb0;C, the overall lifespan of Ent2*/CyO flies was slightly longer than that of the w1118, whereas at 25 &#xb0;C, no significant difference was observed. Regarding locomotor ability, the climbing performance of heterozygous flies was significantly lower than that of the w1118 at both temperatures, with males being more severely affected. In addition, the antioxidant enzyme activities of CAT and SOD in Ent2*/CyO fruit flies were significantly reduced, indicating a clear impairment of antioxidant capacity. These results describe the phenotypic profile of a CRISPR-generated Ent2 mutant line and demonstrate the feasibility of combining genome editing with balancer chromosome strategies in Drosophila. This study provides a methodological framework and a genetic resource for future investigations of genes associated with metabolism and environmental responses.

Animals↗
PubMed2006

A framework to monitor environment-induced major genes for developmental trajectories: implication for a prenatal cocaine exposure study.

Whether there are specific genes involved in response to different environmental agents and how such genes regulate developmental trajectories during lifetime are of fundamental importance in health, clinical and pharmaceutical research. In this article, we present a novel statistical model for monitoring environment-induced genes of major effects on longitudinal outcomes of a trait. This model is derived within the maximum likelihood framework, incorporated by mathematical aspects of growth and developmental processes. A typical structural model is implemented to approximate time-dependent covariance matrices for the longitudinal trait. This model allows for a number of biologically meaningful hypothesis tests regarding the effects of major genes on overall growth trajectories or particular stages of development. It can be used to test whether and how major genetic effects are expressed differently under altered environmental agents. In a well-designed case-control study, our model has been employed to detect cocaine-dependent genes that affect growth trajectories for head circumference during childhood. The detected gene triggers significant effects on growth curves in both cocaine-exposed (case) and unexposed groups (control), but with different extents. Significant genotype-environment interactions due to this so-called environment-sensitive gene are promising for further studies toward its genomic mapping using polymorphic molecular markers.

Adult↗
PubMed2006

[Characteristics of acid-base balance in patients with chronic severe hepatitis: analysis of 126 cases].

OBJECTIVE: To investigate the characteristics of acid-base balance in patients with chronic severe hepatitis. METHODS: Samples of venous blood and arterial blood were collected from 126 patients with chronic severe hepatitis, 106 males and 20 females, aged 44 +/- 13 (25 - 74), to undergo measurement of the potassium, sodium, and chloride ions, and urea nitrogen and creatine, blood electrolytes and blood gas analysis respectively. RESULTS: Acid-base disturbance (ABD) was found in 115 of the 126 patients (91.3%). 40 of the 115 patients with ABD (31.7%) had respiratory alkalosis combined with metabolic alkalosis, 32 of them (25.4%) had respiratory alkalosis combined with metabolic acidosis; 28 of them (22.2%) had pure respiratory alkalosis, and 8 (6.3%) had pure metabolic acidosis. Five patients had triple acid-base disturbance, 4 of which had respiratory alkalosis (combined with metabolic alkalosis and metabolic acidosis, 3.2%), and 1 of which had respiratory acidosis (combined with metabolic alkalosis and metabolic acidosis, 0.8%). There was no significantly difference in the prevalence rates of pure acid-base disturbance and multiple acid-base disturbances between the patients with cirrhosis-base chronic severe hepatitis and those with chronic hepatitis-based chronic severe hepatitis. Hypoxia symptoms were seen in 34 patients (27%). 103 patients died. All the 15 patients with their blood pH < 7.35 died. CONCLUSION: ABD in the patients with chronic severe hepatitis is mainly alkalosis with respiratory alkalosis as the basic ABD type. The appearance of ABD is not associated with the underlying illness. Patients of chronic severe hepatitis often suffer from hypoxia. Low blood pH is an important factor causing death.

Acid-Base Imbalance↗
PubMed2006

Inhibition of hepatitis B virus X gene expression by 10-23 DNAzymes.

The X protein (HBx) of human hepatitis B virus (HBV) is a transcriptional activator protein. The HBx protein plays an important role in viral replication in HBV infected cells and the liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Therefore, the repression of HBx gene expression by 10-23 DNAzymes might be a good way to inhibit HBV replication and counteract HBV-related liver diseases. We designed three 10-23 DNAzymes with different substrate-recognition domains. When each of the 10-23 DNAzymes were cotransfected into human AD293 cells with HBx-EGFP expression plasmid, they could all reduce the level of HBx mRNA as well as the HBx-EGFP protein. These results suggest that the 10-23 DNAzymes might be used for gene therapy of liver diseases caused by HBV.

Antiviral Agents↗
PubMed2006

A statistical model to analyse quantitative trait locus interactions for HIV dynamics from the virus and human genomes.

Viruses can be considered 'parasites' because they cannot survive outside of a host. The progression rate to AIDS caused by human immunodeficiency virus type-1 (HIV-1) is therefore a consequence of HIV-host cell interactions. In this article, we present an innovative statistical model for detecting the effects of genetic interactions on HIV-1 dynamics triggered by different quantitative trait loci (QTL) from the HIV and human genomes. Our model integrates the principles of functional mapping for longitudinal traits and of linkage disequilibrium analysis for high-resolution mapping of QTL within the maximum likelihood context and is implemented with the EM algorithm. We performed Monte Carlo simulation studies to investigate the impacts of different heritability levels and sample sizes on the power to detect interacting QTL. Our model allows for the tests of a number of clinically meaningful hypotheses and provides a powerful tool for unravelling the genetic architecture of HIV-1 dynamics and therefore AIDS progression rate.

Algorithms↗
PubMed2006

Predicting caregiver-reported behavior problems in cocaine-exposed children at 3 years.

Predictors of caregiver-reported behavior problems for 3-year-olds with prenatal cocaine exposure (PCE) and matched controls were examined using structural equation modeling. We tested whether PCE had a direct effect on child behavior problems in a model that included other prenatal drug exposure, child sex, caregiver depression, and the quality of the child's home environment. The sample (N = 256) was drawn from a longitudinal, prospective study of children of (predominantly crack) cocaine-using women and controls matched on race, socioeconomic status, parity, and pregnancy risk. Child Behavior Problems was modeled as a latent variable composed of the 48-item Conners' Parent Report Scale Conduct Problem and Impulsive-Hyperactive scales and the Eyberg Child Behavior Inventory Intensity scale. Caregiver depression was the only significant predictor of Child Behavior Problems. Mean levels of caregiver self-reported depression and reported child behavior problems did not differ between groups. Mean depression scores were well above the recommended clinical cutoff while mean child behavior problems scores were within normal limits. The model explained 21% of the variance in caregiver-reported child behavior problems in our sample of rural African American, low SES youngsters. Non-maternal caregivers of cocaine-exposed children had significantly lower mean depression scores and mean child behavior problems ratings for 2 of 3 scales used in the study compared to biological mothers of children with PCE and controls. For all groups, much larger proportions of children were rated as having clinically significant behavior problems than would be expected based on the prevalence of behavior problems in the general population.

Caregivers↗
PubMed2006

Retrospective survey of 452 patients with inflammatory bowel disease in Wuhan city, central China.

BACKGROUND: Inflammatory bowel disease (IBD) had been uncommon in China until about 1990, but since then, it has been seen in the clinical setting more and more. The prevalence and phenotype of IBD in the Chinese population is not well known. The present study investigates the trend of prevalence in ulcerative colitis (UC) and Crohn's disease (CD) in Wuhan City, central China, and evaluates clinical features, extraintestinal manifestations, and the treatment of IBD in the last 14 years. METHODS: Three hundred and eighty-nine patients with UC and 63 patients with CD were retrospectively collected from 5 central hospitals in Wuhan City, in which high-quality endoscopic and histological diagnoses were available from 1990 to 2003. UC and CD were diagnosed based on clinical, experimental, radiological, endoscopic, and histological examinations according to the internationally accepted Lennard-Jones criteria. RESULTS: The trend toward prevalence of UC and CD increased between 1990 and 2003 in Wuhan City. There was no change in the sex and age distribution comparing 1990 to 1996 with 1997 to 2003 both in UC and CD. However, the number of individuals with higher education and a professional occupation during 1997 to 2003 was significantly higher than that during the period 1990 to 1996 in patients with UC (OR 2.1, 95% CI 1.27-3.35, P = 0.004; OR 2.2, 95% CI 1.31-3.61, P = 0.003). The mean age of patients with CD was significantly younger than that of UC at the time of diagnosis (32.6 +/- 12.5 vs. 42 +/- 14.5, P < 0.0001). The ratio of male to female patients was 1.53:1 in UC and 2.32:1 in CD, respectively. The mean duration of onset of the disease to diagnosis was 1.4 years in UC and 1.1 years in CD. The extra intestinal manifestations of UC and CD were 5.7% and 19%, respectively, and complications of UC and CD were 6.4% and 50.8%, respectively. Only 3% of UC patients required surgery, whereas 27% of CD patients underwent surgical procedures (P < 0.001). CONCLUSION: The prevalence of IBD has increased in Wuhan City, central China, but is not as high as in Western countries. The disease in Wuhan City has often been associated with young adult professional males with a high level of education. The clinical presentation of UC was often mild and had few extra intestinal manifestations.

Adolescent↗
PubMed2006

Gastric secretion.

PURPOSE OF REVIEW: To summarize the literature over the past year on the regulation of gastric exocrine and endocrine secretion. RECENT FINDINGS: Gastric acid secretion by parietal cells is precisely regulated by overlapping neural, hormonal, and paracrine pathways, both centrally and peripherally. Too much acid can induce gastroduodenal injury. Too little acid can interfere with the absorption of iron, calcium, vitamin B12, and certain drugs as well as predispose the patient to enteric infection. A number of peptides implicated in the central control of food intake such as ghrelin, orexin, and leptin are present in the stomach and are capable of modulating acid secretion. The precise mechanisms whereby Helicobacter pylori produces perturbations in acid secretion are not precisely known but appear to involve changes in somatostatin and perhaps ghrelin secretion. Both gastrin and gastrin-receptor knockout mice as well as gastrin-overexpressing and cAMP-overexpressing mice develop gastric atrophy; gastric atrophy is associated with antiparietal cell antibodies and may be a model for autoimmune gastritis. SUMMARY: A better understanding of the pathways and mechanisms regulating acid secretion as well as the development of genetically engineered mouse models should lead to new strategies to prevent and treat a variety of gastric disorders, including peptic ulcer disease, neoplasia, and autoimmune gastritis.

Animals↗
PubMed2006

Azospirillum melinis sp. nov., a group of diazotrophs isolated from tropical molasses grass.

Fifteen bacterial strains isolated from molasses grass (Melinis minutiflora Beauv.) were identified as nitrogen-fixers by using the acetylene-reduction assay and PCR amplification of nifH gene fragments. These strains were classified as a unique group by insertion sequence-PCR fingerprinting, SDS-PAGE protein patterns, DNA-DNA hybridization, 16S rRNA gene sequencing and morphological characterization. Phylogenetic analysis of the 16S rRNA gene indicated that these diazotrophic strains belonged to the genus Azospirillum and were closely related to Azospirillum lipoferum (with 97.5 % similarity). In all the analyses, including in addition phenotypic characterization using Biolog MicroPlates and comparison of cellular fatty acids, this novel group was found to be different from the most closely related species, Azospirillum lipoferum. Based on these data, a novel species, Azospirillum melinis sp. nov., is proposed for these endophytic diazotrophs of M. minutiflora, with TMCY 0552(T) (=CCBAU 5106001(T) = LMG 23364(T) = CGMCC 1.5340(T)) as the type strain.

Acetylene↗
PubMed2006

Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children.

BACKGROUND: Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. METHODS: Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). RESULTS: Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. CONCLUSIONS: Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.

Child↗
PubMed2006

[Inhibition of hepatitis B virus S gene and C gene expression by different 10-23 DNAzymes substrate-recognition domains].

OBJECTIVE: To explore the inhibition effects of 10-23 DNAzymes with different substrate-recognition domains targeting hepatitis B virus (HBV) S gene and C gene expression in 2.2.15 cells. METHODS: 10-23 DNAzymes with different substrate-recognition domains specific to HBV S gene open reading frame (ORF) A(157)UG and HBV C gene ORF A(1816)UG were designed and synthesized, respectively. Different 10-23 DNAzymes were transfected into 2.2.15 cells which is a stable HBV producing cell line. HBsAg and HBeAg secreted into culture media were detected by radioimmunoassay (RIA) and HBV DNA levels were measured by real-time PCR. 3-(4, 5-dimethylthiagol-2-yl)-2, 5-drphnyl tetrazolium bromide (MTT) assays were performed to evaluate cytotoxicity. RESULTS: HBsAg and HBeAg expressions were reduced by various DNAzymes (0.1 - 2.5 micromol/L) with different substrate-recognition domains after transfection. The antiviral effects of DNAzymes were apparent until 72 h post-transfection. The inhibition rates of the DNAzymes at the same dose on HBsAg and HBeAg in the same period of post-transfection were as the following: DrzBS-9 > DrzBS-8 > DrzBS-7; DrzBC-9 > DrzBC-8 > DrzBC-7. Among all the DNAzymes used, DrzBS-9 targeting S gene and DrzBC-9 targeting C gene were most potent, with HBsAg and HBeAg reduced 95% and 92% 48 h post-transfection at the dose of 2.5 micromol/L, respectively. The inhibition effects on HBV DNA by various DNAzymes with different substrate-recognition domains were of no significance. There were no evident cytotoxic effects of these DNAzymes in the range from 0.1 to 2.5 micromol/L. CONCLUSION: 10-23 DNAzymes with different substrate-recognition domains targeting HBV S gene and C gene mRNA possessed specific inhibition effects in 2.2.15 cells, and DrzBS-9 targeting S gene and DrzBC-9 targeting C gene were most potent.

Cell Line↗
PubMed2005

Structured antedependence models for functional mapping of multiple longitudinal traits.

In this article, we present a statistical model for mapping quantitative trait loci (QTL) that determine growth trajectories of two correlated traits during ontogenetic development. This model is derived within the maximum likelihood context, incorporated by mathematical aspects of growth processes to model the mean vector and by structured antedependence (SAD) models to approximate time-dependent covariance matrices for longitudinal traits. It provides a quantitative framework for testing the relative importance of two mechanisms, pleiotropy and linkage, in contributing to genetic correlations during ontogeny. This model has been employed to map QTL affecting stem height and diameter growth trajectories in an interspecific hybrid progeny of Populus, leading to the successful discovery of three pleiotropic QTL on different linkage groups. The implications of this model for genetic mapping within a broader context are discussed.

Journal Article↗
PubMed2005

A hyperspace model to decipher the genetic architecture of developmental processes: allometry meets ontogeny.

To better utilize limited resources for their survival and reproduction, all organisms undergo developmental changes in both body size and shape during ontogeny. The genetic analysis of size change with increasing age, i.e., growth, has received considerable attention in quantitative developmental genetic studies, but the genetic architecture of ontogenetic changes in body shape and its associated allometry have been poorly understood partly due to the lack of analytical tools. In this article, we attempt to construct a multivariate statistical framework for studying the genetic regulation of ontogenetic growth and shape. We have integrated biologically meaningful mathematical functions of growth curves and developmental allometry into the estimation process of genetic mapping aimed at identifying individual quantitative trait loci (QTL) for phenotypic variation. This model defined with high dimensions can characterize the ontogenetic patterns of genetic effects of QTL over the lifetime of an organism and assess the interplay between genetic actions/interactions and phenotypic integration. The closed forms for the residual covariance matrix and its determinant and inverse were derived to overcome the computational complexity typical of our high-dimensional model. We used a worked example to validate the utility of this model. The implications of this model for genetic research of evo-devo are discussed.

Algorithms↗
PubMed2005

Development of simplified vasoactive intestinal peptide analogs with receptor selectivity and stability for human vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors.

Vasoactive intestinal peptide (VIP) is a widespread neurotransmitter whose physiological and pathophysiological actions are mediated by two receptor classes, VIP/pituitary adenylate cyclase-activating polypeptide (VPAC) 1 and VPAC2. VIP is a 28-amino acid peptide that is rapidly degraded and simplified; metabolically stable analogs are needed. In this study, we use information from studies of the VIP pharmacophore for VPAC1/VPAC2 to design nine simplified VIP analogs that could have high affinity and selectivity for each VPAC or that retained high affinity for both VPACs and were metabolically stable. From binding studies of their abilities to directly interact with hVPAC1 (T47D cells, hVPAC1-transfected cells) and hVPAC2 (Sup T1- and VPAC2-transfected cells) and to stimulate adenylate cyclase in each, two analogs [(Ala(2,8,9,11,19,22,24,25,27,28))VIP and (Ala(2,8,9,11,19,24-28))VIP] were found to have >2000- and >600-fold selectivity for hVPAC1. None of the nine analogs had hVPAC2 selectivity. However, two simplified analogs [(Ala(2,8,9,16,19,24))VIP and (Ala(2,8,9,16,19,24,25))VIP] retained high affinity and potency for both hVPACs. 125I-[Ala(2,8,9,16,19,24,25)]VIP was much more metabolically stable than 125I-VIP. The availability of these simplified analogs of VIP, which are metabolically stable and have either hVPAC1 selectivity or retain high affinity for both hVPACs, should be useful for exploring the role of VPAC subtypes in mediating VIPs' actions as well as being useful therapeutically and for exploring the usefulness of VIP receptor imaging of tumors and VIP receptor-mediated tumor cytotoxicity.

Amino Acid Sequence↗
PubMed2005

Functional mapping of quantitative trait loci that interact with the hg mutation to regulate growth trajectories in mice.

The high growth (hg) mutation increases body size in mice by 30-50%. Given the complexity of the genetic regulation of animal growth, it is likely that the effect of this major locus is mediated by other quantitative trait loci (QTL) with smaller effects within a web of gene interactions. In this article, we extend our functional mapping model to characterize modifier QTL that interact with the hg locus during ontogenetic growth. Our model is derived within the maximum-likelihood context, incorporated by mathematical aspects of growth laws and implemented with the EM algorithm. In an F2 population founded by a congenic high growth (HG) line and non-HG line, a highly additive effect due to the hg gene was detected on growth trajectories. Three QTL located on chromosomes 2 and X were identified to trigger significant additive and/or dominant effects on the process of growth. The most significant finding made from our model is that these QTL interact with the hg locus to affect the shapes of the growth process. Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals.

Age Factors↗