Search

Background and Purpose: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro‐immune communication. Neuronal mechanism‐based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro‐immune mechanism. Experimental Approach: Pharmacological intervention, immunofluorescence, RNA‐sequencing, genetic modification and immunoassay were performed to dissect the neuro‐immune basis of itch and inflammation in atopic dermatitis‐like mouse model and in patients. Key Results: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)‐induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX‐314, a charged NaV blocker that enters through pathologically activated large‐pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV1.8‐expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1‐positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity‐dependent release of calcitonin gene‐related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. Conclusion and Implications: NaV1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti‐inflammatory and anti‐pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis. [ABSTRACT FROM AUTHOR]

We compared the photosynthetic characteristics in relation to yield of two F1 cotton hybrids (Shiza 2-F1 and Xinluzao 43-F1), their parental lines (NT2, H2 and 4-14) and their F2 descendants at different growth and development stages. The two F1 exhibited heterobeltiosis in net photosynthetic rate (Pn) by 8.1-52.1%, canopy apparent photosynthetic rate (CAP) by 8.2-57.6% and canopy respiration rate (CR) by 3.0-78.7% during the growing season. They also exhibited mid-parent heterosis by 2.0-5.2% in leaf chlorophyll content (SPAD) during the late growth and development stages. Regression analysis showed that both parents contributed to increase in Pn, SPAD and CAP in the F1. A low CR in the F1 matched a low CR of the parental line. Photosynthetic characteristics in the F2 were mainly dependent upon the magnitude and degeneration rate of the F1. Mid-parent heterosis in CAP and in CR during the late growth and development stage reduced the degeneration of the F2. Average dry matter accumulation was 10.7-34.7% higher in the parental lines of Xinluzao 43-F1 than in the parental lines of Shiza 2-F1. Heterobeltiosis in dry matter accumulation was 7.0-23.1% greater for Xinluzao 43-F1 than for Shiza 2-F1. Dry matter accumulation in the F1 was affected by either the dry matter accumulation of parents or heterobeltiosis. Dry matter accumulation in the F2 was mainly influenced by dry matter accumulation in the F1. The yields of the two F1 were 39.1-46.3% higher than their respective parents and 26.4-45.9% higher than that of the conventional cultivar Xinluzao 33. The yields of the two F2 were 9.2-12.8% higher than the parents and 14.9-27.4% higher than that of Xinluzao 33. The photosynthetic production and yield of the F1 and F2 were higher than that of their parents. The increases in Pn and CAP of the F1 and F2 were dependent on the photosynthetic characteristics of their parents. It is thus concluded that the photosynthetic performance, light use efficiency and yield of the F1 can be improved by using at least one parent with low CR, but high CAP, Pn and SPAD. This strategy might also improve the value of the F2.

A multi-dimensional earthquake isolation and mitigation device for long-span reticulated structures is a type of newly invented passive control device. In order to acquire the earthquake isolation and mitigation effect of the new devices on long-span reticulated structures under horizontal excitations, the pseudo-dynamic tests for a 1:3 modeled long-span reticulated structure with a size of 3 m × 3 m with and without the devices are carried out. Horizontal dynamic responses of the structure with and without the devices are compared, and the earthquake isolation and mitigation effect of the devices is evaluated under the horizontal excitations. It can be shown from the experimental and finite element numerical results that the proposed new devices have a good effect on earthquake isolation and mitigation on long-span reticulated structures under horizontal earthquake excitations. [ABSTRACT FROM PUBLISHER]

To reevaluate the association between the costimulatory molecule cytotoxic T lymphocyte-associated antigen4 ( CTLA4) single nucleotide polymorphism (SNP) +49A/G and acute rejection (AR) in renal transplantation, nine studies published before June 2013 were analyzed. Meta-analysis and cumulative meta-analysis (metacum) were performed for each genotype in a random/fixed effect model. The combined odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. In the sensitivity analysis, a single study involved in the meta-analysis was deleted each time to investigate the influence of the individual data sets on the pooled ORs. Meta-analysis regression was used for some influence factors, such as year of publication, total number in each group (AR group and control group), ethnicity, the ratio of GG to GA + AA, the ratio of G to A in CTLA4 +49A/G. Overall, a significant correlation was noted between the CTLA4 SNP (+49A/G) and the risk of AR (for GG vs. AG + AA: OR = 1.35, 95% CI = 1.05-1.73, p = 0.02; for G vs. A: OR = 1.21, 95% CI = 1.03-1.42, p = 0.02), especially in the Asian subgroup (for GG vs. AG + AA: OR = 1.79, 95% CI = 1.15-2.78, p = 0.009; for G vs. A: OR = 1.47, 95% CI = 1.04-2.07, p = 0.03). Of the influence factors, the ratio of GG to GA+AA ( p = 0.046) and the ratio of G to A ( p = 0.017) were significant factors. In conclusion, our results suggest that CTLA4 +49A/G contribute to the risk of AR following renal transplantation. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transplantation (RT) recipients who underwent a 192-month follow-up. Multivariate analyses revealed that recipient rs231775 genotype is significantly associated with tumorigenesis (P=0.012). Multiplicative interaction between rs231775 AA and possible risk factors of malignancy revealed two significant results: rs231775 AA × primary diseases and rs231775 AA × number of HLA-mismatch. The frequency of haplotype TACAG was significantly higher in the tumor group (17.07%) than that in the nontumor group (1.53%). In addition, aristolochic acid nephropathy (P=0.003) and the time of discovery of tumor (P=0.000) also were independently associated with tumorigenesis. Our data show that the CTLA4 genotype rs231775 AA may be one of risk factors for the development of malignancy and haplotype TACAG was susceptible haplotype in Chinese kidney transplant recipients. [ABSTRACT FROM AUTHOR]

The earthquake excitation is a complicated multidimensional motion, which will cause the damage or even collapse of structures. Consequently, some measures to prevent structure failure must be taken under multidimensional excitations, especially for long-span reticulated structures and high-rise buildings. Many earthquake isolation or mitigation devices have been manufactured to reduce the horizontal dynamic responses of structures, but there are few reports concerning the device isolating and mitigating earthquake actions both in horizontal and vertical directions simultaneously. In this paper, a new multidimensional earthquake isolation and mitigation device for long-span reticulated structures is developed and tested under different cases. Effects of excitation frequency and amplitude on vertical properties of this device are studied. Then, the modified equivalent standard solid model is proposed to describe the vertical properties of the device. Experimental and numerical studies show that this device has good capability of energy dissipation in vertical direction. [ABSTRACT FROM PUBLISHER]

Prostate Cancer has become the second leading cause of male cancer-related incidence and mortality in United States. Hyperthermia (HT) is known to serve as a powerful tool in treatment of prostate cancer in clinical. The combination treatment with HT and cisplatin has a synergistic effect to inhibit prostate cancer progression and demonstrates better clinical effectiveness than HT or chemotherapy alone. But molecular mechanisms of this phenomenon have not been illuminated clearly. In this study, we used MTS assay to examine cell viabilities of PC-3, LNCaP, DU-145 and RM-1 cells after treated by HT and cisplatin. Then colony formation of PC-3 and DU-145 cells after treated with HT and cisplatin were photographed. To investigate whether the combination therapy would enhance apoptosis of PC-3 and DU-145 cells, we used Western blot analysis to detect expression level of proteins on apoptosis-regulated signaling pathway in PC-3 and DU-145 cells. Our results showed that the combination treatment decreased cell viabilities and colony formation of prostate cancer cells in a dose-dependent manner and this combination therapy enhanced apoptosis of PC-3 and DU-145 cells via activation of Caspase-3 and cleavage of PARP. We also found that the combination therapy could down-regulate the anti-apoptotic Bcl-2 and IAP family proteins. At last, the combination therapy activated AMPKα-JNK signaling pathway and inhibited Akt-mTOR-p70s6k signaling pathway to promote apoptosis of PC-3 and DU-145 cells. In conclusion, this study clearly elucidated how the combination therapy with HT and cisplatin promoted apoptosis of prostate cancer cells in synergy. [ABSTRACT FROM AUTHOR]

Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A, rs3087243G/A) on the early acute rejection (AR) of Chinese deceased donor renal transplantation recipients. Genotyping of the CTLA4 SNPs was performed in 167 deceased donor renal transplantation recipients. Each patient underwent a 6-month follow-up observation for AR. The incidence of AR during the 6 months post-transplantation was 26.9% (45 out of 167 patients). Patients experiencing AR were found to have a higher frequency of the rs733618TT genotype and T allele (p=0.000 and p=0.002, respectively). While the haplotype CACAG was merely observed in non-AR group (corrected p=0.000), the frequency of haplotype TACGG was significantly higher in AR group than in non-AR group even after 50,000 permutation tests (corrected p=0.018). In conclusion, these polymorphisms statistically significantly associated with acute renal allograft rejection may be considered as a risk factor of AR in Chinese renal transplantation recipients except for haplotype CACAG as a protective one., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.