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SUMMARY: Studies evaluating the association of Interleukin 10 (IL-10) polymorphisms with risk of pediatric asthma found inconsistent data. Here, we performed a meta-analysis to get a precise estimation of the associations. Relevant studies identified in the PubMed, Scopus, CNKI databases were used to perform a meta-analysis. A total of 23 case-control studies including nine studies with 1298 cases and 1079 controls on IL-10-1082G>A, four studies with 622 cases and 603 controls on -819C>T and ten studies with 1480 case and 1462 controls on -592C>A were selected. Overall, there was no significant association between IL-10 polymorphisms with pediatric asthma risk in global population. When stratified by ethnicity, there was a significant association of IL-10-1082G>A with pediatric asthma in Asians and Chinese. This meta-analysis result revealed that IL-10-1082G>A, -819C>T and -592C>A polymorphisms were not associated with pediatric asthma risk in the global population.

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Cadmium (Cd) is highly toxic to the environment and humans. Plants are capable of absorbing Cd from the soil and of transporting part of this Cd to their shoot tissues. In Arabidopsis, the plasma membrane Heavy Metal ATPase 4 (HMA4) transporter mediates Cd xylem loading for export to shoots, in addition to zinc (Zn). A recent study showed that di-Cys motifs present in the HMA4 C-terminal extension (AtHMA4c) are essential for high-affinity Zn binding and transport in planta. In this study, we have characterized the role of the AtHMA4c di-Cys motifs in Cd transport in planta and in Cd-binding in vitro. In contrast to the case for Zn, the di-Cys motifs seem to be partly dispensable for Cd transport as evidenced by limited variation in Cd accumulation in shoot tissues of hma2hma4 double mutant plants expressing native or di-Cys mutated variants of AtHMA4. Expression analysis of metal homeostasis marker genes, such as AtIRT1, excluded that maintained Cd accumulation in shoot tissues was the result of increased Cd uptake by roots. In vitro Cd-binding assays further revealed that mutating di-Cys motifs in AtHMA4c had a more limited impact on Cd-binding than it has on Zn-binding. The contributions of the AtHMA4 C-terminal domain to metal transport and binding therefore differ for Zn and Cd. Our data suggest that it is possible to identify HMA4 variants that discriminate Zn and Cd for transport.

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Objective To explore the diagnostic value of the quantitative detection of plasma miRNA-125b and miRNA-133b in children with asthma.Methods Thirty asthmatic patients were enrolled in this study and collected the blood specimens during acute phase and stable phase respectively (AP group and SP group).Thirty allergic rhinitis children (AR group) and thirty healthy children were recruited to the control group (NC group).The levels of miRNA in different groups were detected by qRT-PCR.The performance of miRNA-125b and miRNA-133b were evaluated by receiver operating characteristic curves (ROC) and the area under the curve (AUC) (95％CI).Results The relative expression of miRNA-125b in AP group and SP group were significantly higher than A R group (t=3.913,3.120,P＜0.01),miRNA-133b.In AP group and AR group the expression of miRNA-133b were significantly higher than control group (t=4.426,4.720,P＜0.01).The detection of miRNA-125b yielded an area under the curve of ROC of 0.7989,(95 ％ CI:0.7111～ 0.8864) in discriminating asthmatic patients from healthy group.And the miRNA-133b was 0.7274 (95％CI:0.586 5～0.863 0) in discriminating asthmatic patients during the acute phase from healthy group.Conclusion The relative expression of miRNA-125b in children with asthma was significantly higher than that in AR group and NC group,miRNA-125b may prove to be a non-invasive biomarker for the auxiliary diagnosis of asthma especially when the relative expression up to 1.998.

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This study links changes in the tobacco endogenous metal-homeostasis network caused by transgene expression with engineering of novel features. It also provides insight into the concentration-dependent mutual interactions between Zn and Cd, leading to differences in the metal partitioning between wild-type and transgenic plants. In tobacco, expression of the export protein AtHMA4 modified Zn/Cd root/shoot distribution, but the pattern depended on their concentrations in the medium. To address this phenomenon, the expression of genes identified by suppression subtractive hybridization and the Zn/Cd accumulation pattern were examined upon exposure to six variants of low/high Zn and Cd concentrations. Five tobacco metal-homeostasis genes were identified: NtZIP2, NtZIP4, NtIRT1-like, NtNAS, and NtVTL. In the wild type, their expression depended on combinations of low/high Zn and Cd concentrations; co-ordinated responses of NtZIP1, NtZIP2, and NtVTL were shown in medium containing 4 µM Cd, and at 0.5 µM versus 10 µM Zn. In transgenics, qualitative changes detected for NtZIP1, NtZIP4, NtIRT1-like, and NtVTL are considered crucial for modification of Zn/Cd supply-dependent Zn/Cd root/shoot distribution. Notwithstanding, NtVTL was the most responsive gene in wild-type and transgenic plants under all concentrations of Zn and Cd tested; thus it is a candidate gene for the regulation of metal cross-homeostasis processes involved in engineering new metal-related traits.

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BACKGROUND: To increase the Zn level in shoots, AtHMA4 was ectopically expressed in tomato under the constitutive CaMV 35S promoter. However, the Zn concentration in the shoots of transgenic plants failed to increase at all tested Zn levels in the medium. Modification of Zn root/shoot distribution in tomato expressing 35S::AtHMA4 depended on the concentration of Zn in the medium, thus indicating involvement of unknown endogenous metal-homeostasis mechanisms. To determine these mechanisms, those metal-homeostasis genes that were expressed differently in transgenic and wild-type plants were identified by microarray and RT-qPCR analysis using laser-assisted microdissected RNA isolated from two root sectors: (epidermis + cortex and stele), and leaf sectors (upper epidermis + palisade parenchyma and lower epidermis + spongy parenchyma). RESULTS: Zn-supply-dependent modification of Zn root/shoot distribution in AtHMA4-tomato (increase at 5 µM Zn, no change at 0.5 µM Zn) involved tissue-specific, distinct from that in the wild type, expression of tomato endogenous genes. First, it is suggested that an ethylene-dependent pathway underlies the detected changes in Zn root/shoot partitioning, as it was induced in transgenic plants in a distinct way depending on Zn exposure. Upon exposure to 5 or 0.5 µM Zn, in the epidermis + cortex of the transgenics' roots the expression of the Strategy I Fe-uptake system (ethylene-dependent LeIRT1 and LeFER) was respectively lower or higher than in the wild type and was accompanied by respectively lower or higher expression of the identified ethylene genes (LeNR, LeACO4, LeACO5) and of LeChln. Second, the contribution of LeNRAMP2 expression in the stele is shown to be distinct for wild-type and transgenic plants at both Zn exposures. Ethylene was also suggested as an important factor in a pathway induced in the leaves of transgenic plants by high Zn in the apoplast, which results in the initiation of loading of the excess Zn into the mesophyll of "Zn accumulating cells". CONCLUSIONS: In transgenic tomato plants, the export activity of ectopically expressed AtHMA4 changes the cellular Zn status, which induces coordinated tissue-specific responses of endogenous ethylene-related genes and metal transporters. These changes constitute an important mechanism involved in the generation of the metal-related phenotype of transgenic tomato expressing AtHMA4.

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The aim of this work was to assess the potential for using AtHMA4 to engineer enhanced efficiency of Zn translocation to shoots, and to increase the Zn concentration in aerial tissues of tomato. AtHMA4, a P1B-ATPase, encodes a Zn export protein known to be involved in the control of Zn root-to-shoot translocation. In this work, 35S::AtHMA4 was expressed in tomato (Lycopersicon esculentum var. Beta). Wild-type and transgenic plants were tested for Zn and Cd tolerance; Zn, Fe and Cd accumulation patterns, and for the expression of endogenous Zn/Fe-homeostasis genes. At 10µM Zn exposure, a higher Zn concentration was observed in leaves of AtHMA4-expressing lines compared to wild-type, which is promising in terms of Zn biofortification. AtHMA4 also transports Cd and at 0.25µM Cd the transgenic plants showed similar levels of this element in leaves to wild-type but lower levels in roots, therefore indicating a reduction of Cd uptake due to AtHMA4 expression. Expression of this transgene AtHMA4 also resulted in distinct changes in Fe accumulation in Zn-exposed plants, and Fe/Zn-accumulation in Cd-exposed plants, even though Fe is not a substrate for AtHMA4. Analysis of the transcript abundance of key Zn/Fe-homeostasis genes showed that the pattern was distinct for transgenic and wild-type plants. The reduction of Fe accumulation observed in AtHMA4-transformants was accompanied by up-regulation of Fe-deficiency marker genes (LeFER, LeFRO1, LeIRT1), whereas down-regulation was detected in plants with the status of Fe-sufficiency. Furthermore, results strongly suggest the importance of the up-regulation of LeCHLN in the roots of AtHMA4-expressing plants for efficient translocation of Zn to the shoots. Thus, the modifications of Zn/Fe/Cd translocation to aerial plant parts due to AtHMA4 expression are closely related to the alteration of the endogenous Zn-Fe-Cd cross-homeostasis network of tomato.

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Ectopic expression in tobacco (Nicotiana tabacum v. Xanthi) of the export protein AtHMA4 (responsible in Arabidopsis for the control of Zn/Cd root to shoot translocation) resulted in decreased Cd uptake/accumulation in roots and shoots. This study contributes to understanding the mechanisms underlying this Cd-dependent phenotype to help predict the consequences of transgene expression for potential phytoremediation/biofortification-based strategies. Microarray analysis was performed to identify metal homeostasis genes that were differentially expressed in roots of Cd-exposed AtHMA4-expressing tobacco relative to the wild type. It was established that down-regulation of genes known to mediate Cd uptake was not responsible for reduced Cd uptake/accumulation in AtHMA4 transformants. The transcript levels of NtIRT1 and NtZIP1 were higher in transgenic plants, indicating an induction of the Fe and Zn deficiency status due to AtHMA4 expression. Interestingly, upon exposure to Cd, genes involved in cell wall lignification (NtHCT, NtOMET, and NtPrx11a) were up-regulated in transformants. Microscopic analysis of roots demonstrated that expression of AtHMA4 caused an induction of cell wall lignification in the external cell layers that was accompanied by enhanced H2O2 accumulation. Further study showed that the concentration of other elements (B, Co, Cu, Ni, Mo, and Zn) was reduced in AtHMA4 transformants in the presence of Cd. In conclusion, due to ectopic expression of 35S::AtHMA4, the physical apoplastic barrier within the external cell layer developed, which is likely to be responsible for the reduction of Cd uptake/accumulation.

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Objective To observe the impacts of Kechuanning on expression of signal transducer and activator of transcription 6 (STAT 6) in CD4+, CD8+T lymphocytes of athma rats induced by virus, and analyze the mechanism of Kechuanning in treating asthma induced by RSV. Methods The PBMC was isolated from the peripheral blood, CD4+T, CD8+T lymphocyte was separated by immunomagnetic beads. The purity and activity of CD4+T and CD8+T lymphocytes were measured by using flow cytometry, trypan-blue dye exclusion test. The protein expression of STAT6 was detected by fluorescence-activated cell sorting. Results The descending progress of the trial were supported by the purity and activity of CD4+T, CD8+T lymphocyte. CD4+T lymphocyte in the asthma model group were increased (P0.05). The expression of the protein of STAT6 in the treated group with Kechuanning decoction were decreased than that in the model group (P0.05). Conclusion Kechuanning decoction could decrease the protein of STAT6 in CD4+, CD8+T lymphocyte, thereby it could regulate the disorder of Th1/Th2, thus prevent and treat the asthmatic attack induced by virus.

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BACKGROUND: Asthma causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough. These symptoms are usually associated with widespread but variable airflow limitation that is partly reversible either spontaneously or with treatment. The inflammation also causes an associated increase in airway resposiveness to a variety of stimuli. METHOD: Of the 403 adult bronchial asthma patients enrolled from March 1992 to March 1994 in Allergy Clinics of Severance Hospital in Yonsei University, this study reviewed the 97 cases to evaluate the treatment effects and to analyse prognostic factors. The patients were classified to five groups according to treatment responses ; group 1 (non control group) : patients who were not controlled during following up, group 2 (high step treatment group) : patients who were controlled longer than 3 months by step 3 or 4 treatment of 'Global initiative for asthma, Global strategy for asthma management and prevention' (NHLBI/UNO) with PFR(%) larger than 8055, group 3 (short term control group) : patients who were controlled less than 1 year by step 1 or 2 treatment of NHLBI/WHO, group 4 (intermediate term control group) : patients who were controlled for more than 1 year but less than 2 years by step 1 or 2 treatment of NHLBI/HNO, group 5 (long term control group). patients who were controlled for more than 2 years by step 1 or 2 treatment of NHHI/WHO. Especially the patients who were controlled more than 1 year with negatively converted methacholine test and no eosinophil in sputum were classified to methacholine negative conversion group. We reviewed patients' history, atopy score, total IgE, specific IgE, methacholine PC2O and Peripheral blood eosinophil counts pulmonary function test steroid doses and aggrevation numbers after treatment. RESULTS: On analysis of 98 patients, 20 cases(20.6%) were classified to group 1, 26 cases(26.8%) to group 2, 23 cases(23.7%) to group 3, 15 cases(15.5%) to group 4, and 13 cases(13.4%) to groups 5. There were no differences of sex, asthma type, family history, smoking history, allergic rhinitis and aspirin allergy among the groups. In long term control group, asthma onset age was younger, symptom duration was shorter, and Initial pulmonary function was better. The long term control group required 1ower amounts of oral steroid, had less aggrevation during first 3months after starting treatment and shorter duration from enrollment to control. Atopy, allergic skin tests sputum and blood eosinophil, total IgE, nonspecific bronchial resposiveness was not significantly different among the groups. Seven out of 28 patients who were controlled more than 1 years showed negatively converted methachloine test and no eosinophils in the sputum. The mean control duration was 20.3α9.7 months and relapse did not occur. CONCLUSION: Patients who had asthma of onset age younger, shorter symptom duration better PFT, lower treatment initial steps, lower amounts of steroid needs and less aggravation numbers after starting treatment were classified in the long term control groups compared to the others.

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