Biomedical subjects

Hong Jiao

Publications and source records attributed to Hong Jiao.

7 recordsLinked to original sources

PubMed2007

The CCHCR1 (HCR) gene is relevant for skin steroidogenesis and downregulated in cultured psoriatic keratinocytes.

The HCR gene, officially called Coiled-Coil alpha-Helical Rod protein 1 (CCHCR1), located within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene for the risk effect. Recently, CCHCR1 was shown to promote steroidogenesis by interacting with the steroidogenic acute regulator protein (StAR). Here, we examined the role of CCHCR1 in psoriasis and cutaneous steroid metabolism. We found that CCHCR1 and StAR are expressed in basal keratinocytes in overlapping areas of the human skin, and CCHCR1 stimulated pregnenolone production in steroidogenesis assay. Overexpression of either the CCHCR1*WWCC risk allele or the non-risk allele enhanced steroid synthesis in vitro. Furthermore, the cytochrome P450scc enzyme was expressed in human keratinocytes and was induced by forskolin, a known activator of steroidogenesis, and forskolin also upregulated CCHCR1. CCHCR1 has an altered expression pattern in lesional psoriatic skin compared to normal healthy skin, suggesting its dysregulation in psoriasis. We found that the expression of CCHCR1 is downregulated twofold at the mRNA level in cultured non-lesional psoriatic keratinocytes when compared to non-psoriatic healthy cells. Our results also suggest a connection between CCHCR1 and vitamin D metabolism in keratinocytes. The expression of the vitamin D receptor (VDR) gene was lower in non-lesional psoriatic keratinocytes than in healthy cells. Furthermore, Vdr expression was downregulated in the keratinocytes of mice overexpressing the CCHCR1*WWCC risk allele when compared to keratinocytes from mice with the non-risk allele of CCHCR1. Finally, we demonstrate that other agents relevant for psoriasis and/or the regulation of steroidogenesis influence CCHCR1 expression in keratinocytes, including insulin, EGF, cholesterol, estrogen, and cyclosporin A. Taken the role of steroid hormones, including vitamin D and estrogen, in cell proliferation, epidermal barrier homeostasis, differentiation, and immune response, our results suggest a role for CCHCR1 in the pathogenesis of psoriasis via the regulation of skin steroid metabolism.

Animals↗

PubMed2006

Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity.

OBJECTIVE: LXRA and LXRB genes regulate adiposity, energy dissipation, as well as glucose and lipid homeostasis in mice. We investigated the LXR genes in human obesity. METHODS: LXRA and LXRB mRNAs were quantified in abdominal subcutaneous adipose tissue of obese and nonobese women. The LXRA and LXRB genes were screened for polymorphisms and common single nucleotide polymorphisms genotyped in obese and nonobese women. RESULTS: Relative LXRA mRNA expression levels were higher in obese women (P=0.03). One LXRA single nucleotide polymorphism, rs2279238, and one common haplotype, CAAGCC, as well as two LXRB single nucleotide polymorphisms, LB44732G>A and rs2695121, were associated with obesity phenotypes (nominal P values of 0.0075, 0.0014, 0.008 and 0.02, respectively). Furthermore, there was evidence of interaction between LXRA and LXRB alleles in determining body mass index. CONCLUSION: Our results support a role for LXRA in human adipose tissue. The nominal associations of LXRA and LXRB alleles with obesity are interesting and should be further investigated in independent data sets.

Adipose Tissue↗

PubMed2005

A common beta2-adrenoceptor gene haplotype protects against obesity in Swedish women.

The beta2-adrenoceptor gene may be of particular importance for human obesity because catecholamines have a central role in energy expenditure both as neurotransmitters and hormones. The gene is highly polymorphic, and individual polymorphisms have previously been examined for their relationship to obesity, but results are conflicting. We performed a haplotype analysis of the beta2-adrenoceptor gene in 1354 women and 421 men, all healthy and at least second generation Scandinavian and with a large interindividual variation in body fat mass. We found three common haplotypes. One of these haplotypes, identified as T, A, C, C at nucleotide positions -47, 46, 79, and 491, was in its homozygote form more common among lean (18%) than obese (13%) women (p = 0.0028), but there was no association with obesity in men (p = 0.47). Women who were homozygous for this haplotype had lower BMI (p = 0.009) and percentage body fat (p = 0.005) in comparison with those having other haplotypes or being heterozygous for TACC. The data suggest an important role of the beta2-adrenoceptor gene in obesity because a common haplotype has recessive protective effects against excess body fat, at least in women.

Adult↗

PubMed2005

The CIDEA gene V115F polymorphism is associated with obesity in Swedish subjects.

The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesity in two independent Swedish samples; the first comprised 981 women and the second 582 men. Both samples display a large variation in BMI. The only detected coding polymorphism encodes an exon 4 V115F amino acid substitution, which is associated with BMI in both sexes (P = 0.021 for women, P = 0.023 for men, and P = 0.0015 for joint analysis). These results support a role for CIDEA alleles in human obesity. CIDEA-deficient mice display higher metabolic rate, and the gene cross-talks with tumor necrosis factor-alpha (TNF-alpha) in fat cells. We hypothesize that CIDEA alleles regulate human obesity through impact on basal metabolic rate and adipocyte TNF-alpha signaling.

Alleles↗

PubMed2005

Modeling local item dependence with the hierarchical generalized linear model.

Local item dependence (LID) can emerge when the test items are nested within common stimuli or item groups. This study proposes a three-level hierarchical generalized linear model (HGLM) to model LID when LID is due to such contextual effects. The proposed three-level HGLM was examined by analyzing simulated data sets and was compared with the Rasch-equivalent two-level HGLM that ignores such a nested structure of test items. The results demonstrated that the proposed model could capture LID and estimate its magnitude. Also, the two-level HGLM resulted in larger mean absolute differences between the true and the estimated item difficulties than those from the proposed three-level HGLM. Furthermore, it was demonstrated that the proposed three-level HGLM estimated the ability distribution variance unaffected by the LID magnitude, while the two-level HGLM with no LID consideration increasingly underestimated the ability variance as the LID magnitude increased.

Data Interpretation, Statistical↗

PubMed2005

[Faster detection of Vibrio parahaemolyticus in foods by FQ-PCR technique].

OBJECTIVE: To establish a rapid and accurate qualitative and quantitative method to detect Vibrio parahaemolyticus in food. METHODS: Primers and Taqman probe were designed according to the sequence of gyrase gene of Vibrio parahaemolyticus. The PCR fragment was cloned into PTM vector and was used as positive template for establishing the criterion curve. The simulated samples, made from negative food samples with Vibrio parahaemolyticus positive strain, were used to evaluate the sensitivity of the PCR reaction. 8 Vibrio parahaemolyticus standard strains and other 24 negative strains (8 strains were Vibrionaceae other than Vibrio parahaemolyticus, the rest 16 strains were none-Vibrionaceae) were treated in the same way to evaluate the specificity. All samples were detected with PE7000 sequence detection system and DA620 fluorescene detection system. RESULTS: FQ-PCR method had good specificity and high sensitivity. All 8 strains of Vibrio parahaemolyticus tested showed positive results while all other 24 strains were negative (8 strains were Vibrionaceae, 16 strain were from different). The correlation was 0.9871 between the concentration of positive template and the quantitative curve circular threshold. The threshold for detecting Vibrio parahaemolyticus in pure culture is 10 cfu/ml, and the threshold is as low as 2 cfu/ml with 16 simulative samples after these samples were incubated for a period of time. By direct quantitative detection for uncultured 16 food samples, the threshold is 100 cfu/g. CONCLUSION: FQ-PCR method has high sensitivity and specificity, and it is a handy and rapid detection method. Comparing with regular PCR method, it is not easily contaminated in operation, and can achieve high sensitivity and specificity with domestic instruments. FQ-PCR method has potential and applied value for detection of pathogenic bacteria in food.

Animals↗

PubMed2004

Transgenic mouse models support HCR as an effector gene in the PSORS1 locus.

Genetic susceptibility for psoriasis is regulated to the greatest extent by the PSORS1 locus. Three psoriasis-associated susceptibility alleles have been identified within it, namely, HLACw6, HCR*WWCC and CDSN*5, but strong linkage disequilibrium between them has made it difficult to distinguish their individual genetic effects, and animal models to study their effects are not known. To study the function of HCR, we engineered transgenic mice with either a non-risk allele of HCR or the HCR*WWCC risk allele under the control of the cytokeratin-14 promoter. These choices were motivated by the apparently dominant effect of PSORS1 on psoriasis susceptibility and the physiological expression of HCR in basal keratinocytes. Transgenic mice appeared phenotypically normal and histologically their skin was indistinguishable from wild-type mice. Expression studies using Affymetrix arrays suggested that the HCR risk allele has specific functional consequences relevant to the pathogenesis of psoriasis. Comparison of gene expression changes between non-risk and risk allele mice revealed similarities to previous observations in human psoriatic skin, including upregulation of cytokeratins 6, 16 and 17 in risk allele mice. We also observed changes in the expression of genes associated with terminal differentiation and formation of the cornified cell envelope. Our results support the concept that HCR may constitute an essential gene in the PSORS1 locus. These observations are also compatible with a model that a susceptibility gene for psoriasis induces changes that are contributory but not sufficient by itself to produce the clinical phenotype.

Animals↗