Quercetin improves immune function in Arbor Acre broilers through activation of NF-κB signaling pathway.

Quercetin, the main component of flavonoids, has a wide range of biological actions. Quercetin can be made into a variety of additives for practice, because of the stable chemical structure and water-soluble derivatives. This study was intended to explore the effects of quercetin on immune function and its regulatory mechanism in Arbor Acre broiler to provide a practical basis for improving poultry immune function and figure out the optimum supplementation as functional feed additives. A total of 240 one-day-old healthy Arbor Acre broilers, similar in body weight, were randomly allotted to 4 treatments with 6 replicates, 10 broilers in each replicate and fed with diets containing quercetin at 0, 0.02, 0.04, and 0.06% for 6 wk. Blood and immune organs (spleen, thymus, and bursa) were collected from chickens at the end of the experiment. Growth performance, immune organs indexes, contents of serum immune molecules, splenic T lymphocyte proliferative responses, and expression of immune related genes were evaluated. The results showed that dietary quercetin had no significant effect (P > 0.05) on growth performance of broilers. Compared with control, 0.06% quercetin supplementation in diet significantly increased spleen index and thymus index (P < 0.05). It also increased the secretion of immune molecules including immunoglobulin A (IgA), interleukin-4 (IL-4) (P < 0.001), immunoglobulin M (IgM) (P = 0.007), complement component 4 (C4) (P = 0.001), and tumor necrosis factor-α (TNF-α) (P < 0.05). On the other hand, 0.02% quercetin supplementation significantly increased complement component 3 (C3) (P < 0.05). Additionally, both 0.04 and 0.06% quercetin supplementation significantly increased expression of TNF-α, TNF receptor associated factor-2 (TRAF-2), TNF receptor superfamily member 1B (TNFRSF1B), nuclear factor kappa-B p65 subunit (NF-κBp65), and interferon-γ (IFN-γ) mRNA (P < 0.05), and expression of NF-κB inhibitor-alpha (IκB-α) mRNA were significantly decreased (P < 0.05). Thus, quercetin improved immune function via NF-κB signaling pathway triggered by TNF-α.

Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han population.

Genome-wide association studies have revealed a large number of genetic-risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases share susceptibility loci. Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A single-nucleotide polymorphisms (SNPs) and atopic dermatitis (AD) in a Chinese Han population. In total, three UBASH3A SNPs (rs11203203, rs3788013 and rs1893592) were genotyped using TaqMan genotyping assays in a Chinese Han population (1012 cases and 1362 controls). Among these SNPs, we selected the SNP rs1893592 with association values of P<5 × 10-2 for AD in the TaqMan genotyping assay data for further replication in the independent Chinese replication samples (1080 cases and 1367 controls) using a Sequenom MassARRAY system. We combined the association results in two stages using meta-analysis. We found that rs1893592 in UBASH3A showed association with AD (P=1.29 × 10-3, odds ratio=1.16). These results showed that UBASH3A gene SNP is associated with susceptibility to AD. Further fine mapping and functional studies will be required to identify true causal variant in the UBASH3A gene and its exact role in the pathogenesis of AD.

Administration of low-dose cyclosporine alone for the treatment of elderly patients with membranous nephropathy.

This study aimed to investigate the effects of administration of low-dose cyclosporine A (CsA) alone and the combination of low-dose CsA and a low-dose hormone for the treatment of elderly patients with membranous nephropathy. We divided 27 patients into two groups as follows: low-dose CsA group (group A) and the group receiving a combination of a low-dose hormone and low-dose CsA (group B). The treatment and follow-up times were ≥ 6 months. We observed no difference in gender, age, serum creatinine levels, estimated glomerular filtration rate (eGFR), and 24-h urinary protein levels between the two groups before treatment; in addition, the rates of complete and partial remission were not different 6 months after treatment. The rate of complications in group B was higher than that in group A (84.6 vs 35.7%, respectively; t = 0.018). While the pretreatment eGFR of patients who achieved remission was significantly higher than that of patients who did not achieve remission, the 24-h urinary protein levels and incidence of hypertension were significantly lower than those of patients who did not achieve remission (t = 0.042, 0.035 and 0.043, respectively). The efficacy of administration of low-dose CsA alone and in combination with a low-dose hormone was similar; the efficacy was related to eGFR, urinary protein levels, and the incidence of hypertension before the treatment. The side effects of administration of CsA alone were significantly lower than those of the combination treatment.

Genetic variant rs4982958 at 14q11.2 is associated with allergic rhinitis in a Chinese Han population running title: 14q11.2 is a susceptibility locus for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most common diseases caused by the combined effects of intrinsic factors (susceptibility genes and immunological status) and the external environment. Analyses of ascendant family history of atopic disease suggest that AR and atopic dermatitis might share a similar genetic background. OBJECTIVE: To conduct a case-control study in a Chinese Han population to evaluate the potential influence of single nucleotide polymorphisms (SNPs) at FLG, 5q22.1, 11q13.5, 14q11.2 and 20q13.33 on AR. METHODS: Ten SNPs--rs11204971 and rs3126085 at FLG, rs10067777, rs7701890, rs13360927, and rs13361382 at 5q22.1, rs6010620 at 20q13.33, rs7936562 and rs7124842 at 11q13.5, and rs4982958 at 14q11.2 were genotyped in 363 cases and 668 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. RESULTS: The T allele of rs4982958 at 14q11.2 was observed to be significantly associated with AR (P = .002, OR = 0.73, P(Bonferront) = .02). Genotype-based association testing revealed that the recessive model might provide the best fit for rs4982958 (P(Bonferroni) = .01). In subphenotype analyses, the rs4982958 T allele was also significantly associated with persistent AR (P = .01) and more than 2 positive skin prick tests (P = .038). CONCLUSION: We identified a novel susceptibility locus 14q11.2 for AR that might bear candidate genes conferring susceptibility to AR and affecting disease phenotypes.

Association between the PD1.3A/G polymorphism of the PDCD1 gene and systemic lupus erythematosus in European populations: a meta-analysis.

BACKGROUND: Linkage studies suggest a locus, SLEB2, involved in susceptibility to systemic lupus erythematosus (SLE) and programmed cell death 1 (PDCD1) gene locates in this region. The association of PDCD1 polymorphism (PD1.3A/G) with SLE has been widely investigated, but there are no unambiguous conclusions. OBJECTIVE: To assess the combined evidence for the association between PD1.3A/G polymorphism and SLE and to summarize the effect size of the polymorphism associated with susceptibility to SLE. METHODS: We surveyed studies on the PD1.3A/G polymorphism and SLE using comprehensive PubMed search up to May 2008. The pooled odds ratio (OR) was calculated using a fixed- or a random-effects model. Heterogeneity was identified by sensitivity analysis and publication bias was examined by funnel plot and Egger's test. We also computed the power for a given number of samples. RESULTS: A total of 20 datasets from eight studies that met our inclusion criteria were included. The studies comprised of a total of 2909 cases and 3995 controls. Stratified meta-analysis demonstrated a significant association between PD1.3A and SLE among non-Spanish European descents [OR, 1.290; 95% confidence interval (95% CI), 1.098-1.516; z = 3.10, P = 0.002], while PD1.3G is the risk allele in Spanish populations (OR = 1.414, 95% CI = 1.075-1.862; z = 2.48, P = 0.013). Both results have sufficient power to support these findings. No publication bias presented in the studies analysed. CONCLUSIONS: This meta-analysis demonstrates a significant association between PD1.3A and SLE among non-Spanish European descents, while a negative association was observed in Spanish population.

A novel frameshift mutation of the EDA1 gene in a Chinese Han family with X-linked hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is a rare skin disease characterized by hypotrichosis, hypodontia and hypohidrosis. HED can be autosomal dominant, autosomal recessive or X-linked. However, X-linked HED (XLHED; OMIM 305100) is the most common form. Mutations within the EDA1 gene, which encodes ectodysplasin-A, are responsible for XLHED. In this study, we investigated the EDA1 gene in a Chinese Han family with XLHED, and found a novel 1-bp deletion mutation (c.952delG) in exon 9 of the EDA1 gene, which results in a frameshift and premature termination codon. This result suggests that the c.952delG mutation of the EDA1 gene is likely to be the disease-causing mutation for XLHED in this family. Our study adds new data to the worldwide knowledge of the molecular basis of XLHED.

Follow-up analysis of 180 Chinese Han families: identification of a novel locus for psoriasis at 2p22.3-11.2.

BACKGROUND: Psoriasis is a common inflammatory and hyperproliferative skin disease. The pathogenesis of psoriasis remains obscure. Family and twin studies have suggested a strong genetic susceptibility to psoriasis. Eight linkage loci (PSORS1-7, PSORS9) were identified and accepted by the OMIM and an additional 16 susceptibility loci have been suggested so far. OBJECTIVES: To investigate further three suggested psoriasis susceptibility loci at 2p22.3-11.2, 13q21-32 and 17q22-25.3 in a Chinese population. Using an expanded sample of 180 Chinese families with psoriasis and improved marker coverage, we verified whether they were Chinese Han psoriasis susceptibility loci. METHODS: In total, 180 Chinese Han families with psoriasis vulgaris (including the 61 families used in the original genome-wide scan and 119 new families) were recruited from the Dermatology Department at the First Hospital Affiliated to Anhui Medical University. Two-point and multipoint parametric and nonparametric linkage (NPL) analyses were performed at 2p, 13q and 17q in the total 180 families as well as the 61 original and 119 new families separately. RESULTS: At the region 2p, a maximum multipoint NPL score of 4.11 was identified at locus D2S337 (P=0.000003), and a maximum multipoint heterogeneity LOD (HLOD) score of 4.93 (alpha=54%) was identified at the same locus in the analysis of the 180 families. However, the analysis of the 180 families did not identify any significant linkage evidence at the region 13q21-32 [a maximum multipoint HLOD score of 0.10 (alpha=7%) and NPL score of 0.95 (P=0.14)] or the region 17q22-25.3 [a maximum multipoint HLOD score of 0.08 (alpha=6%) and NPL value of 0.94 (P=0.14)]. For these two regions, the LOD scores from the 180 families as well as the 119 new families were much smaller than the ones obtained from the original 61 families. CONCLUSIONS: Our study indicates that 2p22.3-11.2 is a novel psoriasis susceptibility locus in the Chinese Han population and confirms that psoriasis is a genetically heterogeneous disease.

The genetic epidemiology of tinea versicolor in China.

To study the clinical and epidemiological profile of Pityriasis versicolor (PV) and to determine the possible genetic model for PV in Chinese Han, we investigated 503 patients with PV who were recruited by a questionnaire method. Statistical analysis, heritability and complex segregation analysis were performed using EPI INFO 6.0, SPSS 10.0, the Falconer method and the SAGE-REGTL programs. In the total 503 PV patients, the mean age of onset was 22.85 +/- 10.36 years. For male and female patients, the peak ages of initial onset were both 20-29 years. A total of 106 (21.1%) patients were reported to have a positive family history of PV. The mean age of onset in males with positive family history was earlier than those with negative family history (t = 3.58, P < 0.01). Higher rate of recurrence and longer duration were seen in the patients with positive family history than those with negative family history. The heritability of PV in first-, second- and third-degree relatives was 48.13%, 40.11% and 27.20% respectively. Based on the REGTL results, the best model was a polygenic additive model for PV.

Childhood psoriasis: a study of 277 patients from China.

OBJECTIVES: Psoriasis is common in childhood. The aim of this study was to present the clinical and epidemiological profile of childhood psoriasis in China. METHODS: A total of 277 childhood psoriasis patients younger than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, spss 10.0 and Falconer's method. RESULTS: The median age was 11 years. The male : female ratio was 1:1.13. The median age of onset was 10 years. Of the patients, 48.7% had previous episodes of psoriasis. Of the 277 children with psoriasis, 68.6% had plaque-type psoriasis, 28.9% had guttate psoriasis, 1.1% presented pustular forms of psoriasis and 1.4% had erythroderma. The extensor surface of the extremities was the most frequently affected site in our patients, followed by the appearance of lesions on the scalp. A positive family history of psoriasis was found in 34.3% patients. The prevalence of psoriasis in first- and second-degree relatives was 7.0% and 1.0%, respectively. The heritability of psoriasis in first- and second-degree relatives was 72.67% and 55.18%, respectively. CONCLUSION: Our epidemiologic studies offer the information about Han Chinese distribution, which provide clues to describe psoriasis in children.

The familial risk of acne vulgaris in Chinese Hans - a case-control study.

BACKGROUND: Acne is a chronic inflammatory disease of the pilosebaceous follicles. Recent studies bring us increasing evidences that hereditary factors play an important but indirect role in acne. OBJECTIVE: To investigate the possible role of genetic factors in the pathogenesis of acne vulgaris in Chinese Han ethnic group. PATIENTS AND METHODS: Volunteers of 975 acne cases and 580 controls were included, contributing 3009 and 1825 first-degree relatives, respectively. One thousand and eighty-five first-degree relatives of acne cases were affected with facial acne. This compared with 223 first-degree relatives of non-acne controls. The odds ratio was used to estimate the relative risk for acne vulgaris associated with having an affected first-degree relative. RESULTS: The risk of acne vulgaris occurring in a relative of a patient with acne vulgaris was significantly greater than for the relative of an unaffected individual (odds ratio 4.05, 95% confidence interval (CI): 3.45-4.76, P<0.001). CONCLUSION: Our study suggests that familial factors are important in determining individual susceptibility to acne vulgaris.

Association of HLA haplotype with alopecia areata in Chinese Hans.

BACKGROUND: Some studies have shown discrepancies in human leucocyte antigen (HLA) associated with alopecia areata (AA) between different ethnic populations. OBJECTIVE: To investigate whether HLA-I, -DQA1 and -DQB1 alleles and the HLA haplotype are associated with AA, and the correlation between the HLA haplotype profile, age of onset and severity of AA in Chinese Hans. METHODS: The polymerase chain reaction-sequence specific primer (PCR-SSP) method was used to analyse the frequencies of HLA class I, -DQA1 and -DQB1 alleles in 192 patients with AA and 252 controls in Chinese Hans. The linkage disequilibrium was calculated using the 2 x 2 table. RESULTS: The 24 two-locus haplotypes [including A*02-B*18, A*02-B*27, A*02-B*52, A*02-Cw*0704, A*02-DQA1*0104, A*02-DQB1*0604, A*02-DQB1*0606, B*18-Cw*0704, B*18-DQA1*0104, B*18-DQA1*0302, B*18-DQB1*0606, B*27-Cw*0704, B*27-DQA1*0104, B*27-DQA1*0302, B*52-Cw*0704, B*52-DQA1*0104, B*52-DQA1*0302, B52-DQB1*0606, Cw*0704-DQA1*0104, Cw*0704-DQA1*0302, Cw*0704-DQB1*0606, DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, DQA1*0302-DQB1*0606 (P<0.05)] were associated with AA, while eight extended haplotypes (A*02-B*18-DQA1*0104, A*02-B*27-DQA1*0104, A*02-B*52-DQA1*0104, A*02-B*52-DQA1*0302, A*02-B*52-DQB1*0606, B*52-Cw*0704-DQA1*0104, B*52-Cw*0704-DQA1*0302, A*02-B*52-DQA1*0302-DQB1*0606) were found to be related to AA in Chinese Hans. Through stratified analysis, we found that the extended haplotype B*52-Cw*0704-DQA1*0302 was related to early onset of AA, and no haplotype was only associated with severe AA. CONCLUSION: This is the first detailed report to elucidate HLA haplotypes associated with AA and that demonstrates the significant HLA haplotypes in Chinese Hans AA. The haplotype B*52-Cw*0704-DQA1*0302 was identified to be related to early onset of AA. Our results provide some information for future research on predisposing genes in HLA regions in Chinese Hans.

Refined localization of a punctate palmoplantar keratoderma gene to a 5.06-cM region at 15q22.2-15q22.31.

BACKGROUND: Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13-8q24.21 and 15q22-15q24. However, no genes for this disease have been identified to date. Objectives To refine the previously mapped regions and to identify the disease gene locus in a four-generation Chinese family with punctate PPK. METHODS: Genetic linkage analysis was carried out in this family using microsatellite markers on chromosomes 8q and 15q. Two-point linkage analysis was performed using Linkage programs version 5.10 and the haplotype was constructed using Cyrillic version 2.02 software. RESULTS: We failed to confirm our previous locus at 8q24.13-8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two-point LOD score of 5.38 at D15S153 (theta = 0.00). Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5.06 cM with the previously reported punctate PPK region. CONCLUSIONS: This study refines a disease gene causing punctate PPK to a 5.06-cM interval at 15q22.2-15q22.31.

Marie Unna hereditary hypotrichosis: report of a Chinese family and evidence for genetic heterogeneity.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder with progressive hair loss starting in early childhood and aggravating at puberty. Several studies have mapped the MUHH gene to chromosome 8p21. Here we report a Chinese MUHH family with variable phenotypes. All affected individuals have anomalies affecting both hair density and hair shafts. Major clinical characteristics, disease history and histological examination support the diagnosis of MUHH, but the features of scarring in this kindred are modest and none of the patients have vertex hair loss, which is in contrast with typical MUHH. We now report genotyping and linkage analysis using 11 polymorphic microsatellite markers spanning the MUHH locus at 8p. Two-point linkage analysis using these markers revealed significant exclusion of this locus (log of the odds scores < - 2) at Theta = 0 indicating that there is a range of clinical presentations in MUHH, and that more than one genetic locus is responsible for the disorder.

Effect of intra-epididymal injection of copper particles on fertility, spermatogenesis, and tissue copper levels in rats.

In male rats, a single injection of 10 mg metallic copper particles in oil into each caput epididymidis induced infertility, whilst leaving mating behaviour and blood testosterone levels unchanged. Fertility tended to recover 5.5 months after the copper treatment. Although the copper content of the caput epididymidis reached a level of around 100 times higher than control values, the serum copper concentration did not rise significantly. This finding and the observation that treated animals gained weight as fast as the controls suggest a low systemic toxicity of this method. The testicular copper concentration was significantly higher than that in controls and different degrees of damage, including vacuolation, karyorrhexis, pyknosis, and cytolysis, were seen mainly in pachytene spermatocytes and early spermatids. Clumps of foreign particles, apparently metallic copper, were found in the interstices of the caput epididymidis together with degenerative changes in the epithelial cells of the caput, suggesting a possible effect of copper on the epididymal epithelium. The viability of epididymal sperm decreased more markedly than the decrease in sperm density. It is therefore most likely that the major cause of infertility after copper injection into the caput epididymidis is a direct inhibitory effect of copper on the sperm, whilst damage to the seminiferous and epididymal epithelial may contribute.