Safety profiles and adverse reactions of azithromycin in the treatment of pediatric respiratory diseases: A systematic review and meta-analysis.

BACKGROUND: Azithromycin (AZM) is an antimicrobial agent and frequently used in the treatment of pediatric respiratory diseases due to its well-recognized clinical efficacy. Despite some favorable findings from many studies, there is a lack of research reports focusing on the safety profiles and adverse reactions. METHODS: The randomized controlled trials of AZM in the treatment of pediatric respiratory diseases on internet databases were searched. The search databases included Chinese CNKI, Wanfang, VIP, PubMed, EMBASE, and Cochrane Library. Two researchers of this study independently assessed the eligibility, risk of bias, and extracted the data. The included literature was meta-analyzed and subgroup analyzed by revman 5.1 software. RESULTS: A total of 14 eligible studies were included. The results of meta-analysis showed that the incidence of adverse reactions after AZM treatment was 24.20%, which was lower than 48.05% in the control group (OR = 0.42, 95% CI 0.12-0.72, P < .001). In the subgroup of sequential therapy, AZM had a lower incidence of adverse reactions in sequential therapy (OR = 0.29, 95% CI 0.09-0.60, P < .001). In the subgroup of intravenous administration, AZM had a lower the incidence of adverse reactions (OR = 0.57, 95% CI 0.12-0.84, P = .003). In the subgroup of oral administration, AZM had a lower the incidence of adverse reactions (OR = 0.45, 95% CI 0.13-0.69 P < .001). Overall, it was also found that the incidence of adverse reactions in the AZM subgroup was significantly lower than that in other treatment subgroup. CONCLUSION: AZM has fewer adverse reactions and better safety profiles, which make AZM a more attractive option in the treatment of pediatric respiratory diseases.

Microarray analysis of differentially expressed gene responses to bisphenol A in Arabidopsis.

Environmental levels of bisphenol A (BPA) are a global concern because the compound can cause damage to reproductive organs, the thyroid gland, and brain tissues at developmental stages. Plants are important in removing BPA from the atmosphere, soil, and water. However, knowledge on the mechanism by which plants respond to this compound is limited. To determine the response mechanism of plants to BPA, we used a microarray system to analyze the gene expression patterns of Arabidopsis thaliana after irrigation with 3.0 mM BPA. We identified 651 genes that were differentially expressed upregulated and 470 genes that were downregulated by BPA. These genes may specifically contribute to BPA uptake, transformation, conjugation, and compartmentation in plants. The potential function of upregulated genes in plant defense against BPA was also determined.

Expression and function of a modified AP2/ERF transcription factor from Brassica napus enhances cold tolerance in transgenic Arabidopsis.

One of the most rapid and effective defensive mechanisms plants have for protecting themselves, from a variety of biotic and abiotic stresses, is the regulation of plant signal transcription factors. AP2/ERF factors play an important role in plant development as well as in hormonal regulation and cold response. Directed evolution is a powerful tool to modify proteins, improving their properties, and for studying their structure-function relations. Here, the transgenic Arabidopsis plants over-expressed a mutant gene, BnaERF-B3-hy15-mu3, which encoded for a factor that exhibited more binding activity with the GCC box element than the wild-type gene BnaERF-B3-hy15 encode factor, and exhibited more freezing tolerance than transgenic plants containing the original BnaERF-B3-hy15 gene. Real-time PCR analyses also revealed that the expression levels of several stress-regulated genes were altered in the over-expressed BnaERF-B3-hy15-mu3 transgenic lines. The BnaERF-B3-hy15 responded to exogenous ABA. Using RT-PCR analysis, the expression of BnaERF-B3-hy15 at different stages and stress treatments were also analyzed.

A novel 5-enolpyruvylshikimate-3-phosphate synthase from Rahnella aquatilis with significantly reduced glyphosate sensitivity.

The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19) is a key enzyme in the shikimate pathway for the production of aromatic amino acids and chorismate-derived secondary metabolites in plants, fungi, and microorganisms. It is also the target of the broad-spectrum herbicide glyphosate. Natural glyphosate resistance is generally thought to occur within microorganisms in a strong selective pressure condition. Rahnella aquatilis strain GR20, an antagonist against pathogenic agrobacterial strains of grape crown gall, was isolated from the rhizosphere of grape in glyphosate-contaminated vineyards. A novel gene encoding EPSPS was identified from the isolated bacterium by complementation of an Escherichia coli auxotrophic aroA mutant. The EPSPS, named AroA(R. aquatilis), was expressed and purified from E. coli, and key kinetic values were determined. The full-length enzyme exhibited higher tolerance to glyphosate than the E. coli EPSPS (AroA(E. coli)), while retaining high affinity for the substrate phosphoenolpyruvate. Transgenic plants of AroA(R. aquatilis) were also observed to be more resistant to glyphosate at a concentration of 5 mM than that of AroA(E. coli). To probe the sites contributing to increased tolerance to glyphosate, mutant R. aquatilis EPSPS enzymes were produced with the c-strand of subdomain 3 and the f-strand of subdomain 5 (Thr38Lys, Arg40Val, Arg222Gln, Ser224Val, Ile225Val, and Gln226Lys) substituted by the corresponding region of the E. coli EPSPS. The mutant enzyme exhibited greater sensitivity to glyphosate than the wild type R. aquatilis EPSPS with little change of affinity for its first substrate, shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP). The effect of the residues on subdomain 5 on glyphosate resistance was more obvious.

Enhanced transformation of TNT by Arabidopsis plants expressing an old yellow enzyme.

2,4,6-Trinitrotoluene (TNT) is released in nature from manufacturing or demilitarization facilities, as well as after the firing or detonation of munitions or leakage from explosive remnants of war. Environmental contamination by TNT is associated with human health risks, necessitating the development of cost-effective remediation techniques. The lack of affordable and effective cleanup technologies for explosives contamination requires the development of better processes. In this study, we present a system for TNT phytoremediation by overexpressing the old yellow enzyme (OYE3) gene from Saccharomyces cerevisiae. The resulting transgenic Arabidopsis plants demonstrated significantly enhanced TNT tolerances and a strikingly higher capacity to remove TNT from their media. The current work indicates that S. cerevisiae OYE3 overexpression in Arabidopsis is an efficient method for the phytoremoval and degradation of TNT. Our findings have the potential to provide a suitable remediation strategy for sites contaminated by TNT.

Stress responses to phenol in Arabidopsis and transcriptional changes revealed by microarray analysis.

Phenols are toxic, environmentally persistent products of the chemical industry that are capable of bioaccumulation and biomagnifications in the food chain. Little is known of how plants respond to this compound. To understand the transcriptional changes under phenol, microarray experiments on Arabidopsis thaliana were performed. Microarray results revealed numerous perturbations in signaling and metabolic pathways. The results indicated that the phenol response was related to reactive oxygen species (ROS) accumulation and oxidative conditions, including ROS generated for pathogen defense.

Analysis of gene expression profile of Arabidopsis genes under trichloroethylene stresses with the use of a full-length cDNA microarray.

Trichloroethylene (TCE) is a widespread and persistent environmental contaminant. Plants are able to take up a range of harmful organic compounds, including some of the most abundant environmental pollutants like TCE. In this study, complementary DNA microarrays were constructed to have a better view of transcript expression in Arabidopsis thaliana during TCE-induced stress. The microarray analysis demonstrated the complexity of gene expression patterns resulting from TCE. A total of 1,020 transcripts were differentially up-regulated by TCE. Those genes might specifically contribute to the TCE transformation, conjugation, and compartmentation in plant. This study provides informative preliminary data for more in-depth analyses of TCE tolerance in Arabidopsis thaliana.

Microarray analysis of the phytoremediation and phytosensing of occupational toxicant naphthalene.

Naphthalene is of global environmental concern because it is assumed to contribute considerably to human cancer risk. Plants are important in removing naphthalene from the atmosphere and soil. However, there remains insufficient knowledge on plant response to this compound. To determine the mechanism of naphthalene uptake and transduction in plants, as well as plant response to this compound, a microarray system was used to analyze gene expression patterns in Arabidopsis thaliana after irrigation with 2.0mM naphthalene. A total of 247 differentially expressed genes were identified as upregulated by naphthalene. These genes might specifically contribute to naphthalene uptake, transformation, conjugation, and compartmentalization in the plant. The potential role of upregulated genes in plant defense to naphthalene and the use of phytosensing for naphthalene detection were also discussed.

Optimizing the binding activity of the AP2/ERF transcription factor with the GCC box element from Brassica napus by directed evolution.

In this study, we cloned the ERF-B3 subfamily transcription factor gene BnaERF-B3-hy15 from Brassica napus L. Huyou15. This 600 bp gene encodes a 199 amino acid classic ethylene responsive factor (ERF), which shown no binding or very weak binding GCC box-binding activity by the yeast one-hybrid assay. We used gene shuffling and the yeast one-hybrid system to obtain three mutated sequences that can bind to the GCC box. Sequence analysis indicated that two residues, Gly156 in the AP2 domain and Phe62 at the N-terminal domain were mutated to arginine and serine, respectively. Changes of Gly156 to arginine and Phe62 to serine increased the GCCbinding activity of BnaERF-B3-hy15 and the alter of Gly156 to arginine changed the AP2-domain structure of BnaERF-B3- hy15.

AtCPK6, a functionally redundant and positive regulator involved in salt/drought stress tolerance in Arabidopsis.

The calcium-dependent protein kinase (CDPK) family is needed in plant signaling during various physiological pathways. The Arabidopsis AtCPK6 gene belongs to the subclass of stress-inducible CDPKs, which is stimulated by salt and osmotic stress. To elucidate the physiological function of AtCPK6, transgenic Arabidopsis plants under the control of double CaMV 35S promoter were obtained. AtCPK6 over-expressing plants showed enhanced tolerance to salt/drought stresses. The elevated tolerance of the AtCPK6 over-expressing plants was confirmed by the change of proline and malondialdehyde (MDA). Real-time PCR analyses revealed that the expression levels of several stress-regulated genes were altered in AtCPK6 over-expressing plants. However, cpk6 mutant displayed no obvious difference with control. These results are likely to indicate that AtCPK6 is functionally redundant and a positive regulator involved in the tolerance to salt/drought stress in Arabidopsis.

OsAREB1, an ABRE-binding protein responding to ABA and glucose, has multiple functions in Arabidopsis.

Expression patterns of OsAREB1 revealed that expression of OsAREB1 gene can be induced by ABA, PEG and heat. Yeast one-hybrid assay demonstrated it can bind to ABA-responsive element (ABRE), which was found in most stress-induced genes. Transgenic Arabidopsis over-expressing OsAREB1 had different responses to ABA and glucose compared to wild-type plants, which suggest OsAREB1 might have a crucial role in these two signaling pathways. Further analysis indicate that OsAREB1 have multiple functions in Arabidopsis. First, OsAREB1 transgenic plants had higher resistance to drought and heat, and OsAREB1 up-regulated the ABA/stress related gene such as RD29A and RD29B. Second, it delayed plant flowering time by down-regulating the expression of flowering-related genes, such as FT, SOC1, LFY and AP1. Due to the dates, OsAREB1 may function as a positive regulator in drought/heat stresses response, but a negative regulator in flowering time in Arabidopsis. [BMB reports 2010; 43(1): 34-39].

Over-expression of ThpI from Choristoneura fumiferana enhances tolerance to cold in Arabidopsis.

Thermal hysteresis proteins (Thps) known as antifreeze proteins for their antifreeze activity, depress the freezing point of water below the melting point in many polar marine fishes, terrestrial arthropods and plants. For the purpose of breeding cold-resistant plants, we designed to introduce the Thp gene into the plants. The physiological and biochemical effect of high-lever expression of the modified Choristoneura fumiferana Thp (ThpI) in Arabidopsis thaliana plants was analyzed. Under low temperature stress, the ThpI transgenic plants exhibited stronger growth than wild-type plants. The elevated cold tolerance of the ThpI over-expressing plants was confirmed by the changes of electrolyte leakage activity, malonyldialdehyde and proline contents. These results preliminarily showed that the Thp possibly be used to enhance the low temperature-tolerant ability of plants.

Yeast copper-dependent transcription factor ACE1 enhanced copper stress tolerance in Arabidopsis.

Copper is essential but toxic in excess for aerobic organisms. Yeast transcription factor ACE1 functions as a sensor for copper and an inducer for the transcription of CUP1. In addition, ACE1 can activate the transcription of superoxide dismutase gene (sod1) in response to copper. In this study, we introduced the yeast ACE1 into Arabidopsis and analyzed its function in plant. Under high copper stress, the transgenic plants over-expressing ACE1 showed higher survival rate than the wild-type. We also found that over-expression of ACE1 in Arabidopsis increased the activities of SOD and POD, which were beneficial to the cell in copper buffering. Excess copper would suppress the expression of chlorophyll biosynthetic genes in Arabidopsis, RT-PCR analysis revealed that over-expression of ACE1 decrease the suppression. Together, our results indicate that ACE1 may play an important role in response to copper stress in Arabidopsis.

Expression of a rice DREB1 gene, OsDREB1D, enhances cold and high-salt tolerance in transgenic Arabidopsis.

OsDREB1D, a special DREB (dehydration responsive element binding protein) homologous gene, whose transcripts cannot be detected in rice (Oryza sativa L), either with or without stress treatments, was amplified from the rice genome DNA. The yeast one-hybrid assay revealed that OsDREB1D was able to form a complex with the dehydration responsive element/C-repeat motif. It can also bind with a sequence of LTRE (low temperature responsive element). To analyze the function of OsDREB1D, the gene was transformed and over-expressed in Arabidopsis thaliana cv. Columbia. Results indicated that the over-expression of OsDREB1D conferred cold and high-salt tolerance in transgenic plants, and that transgenic plants were also insensitive to ABA (abscisic acid). From these data, we deduced that this OsDREB1D gene functions similarly as other DREB transcription factors. The expression of OsDREB1D in rice may be controlled by a special mechanism for the redundancy of function.

Gene duplication and transfer events in plant mitochondria genome.

Gene or genome duplication events increase the amount of genetic material available to increase the genomic, and thereby phenotypic, complexity of organisms during evolution. Gene duplication and transfer events have been important to molecular evolution in all three domains of life, and may be the first step in the emergence of new gene functions. Gene transfer events have been proposed as another accelerator of evolution. The duplicated gene or genome, mainly nuclear, has been the subject of several recent reviews. In addition to the nuclear genome, organisms have organelle genomes, including mitochondrial genome. In this review, we briefly summarize gene duplication and transfer events in the plant mitochondrial genome.

Lead induced changes in the growth and antioxidant metabolism of the lead accumulating and non-accumulating ecotypes of Sedum alfredii.

The phytotoxicity and antioxidative adaptations of lead (Pb) accumulating ecotype (AE) and non-accumulating ecotype (NAE) of Sedum alfredii Hance were investigated under different Pb treatments involving 0, 0.02 mmol/L Pb, 0.1 mmol/L Pb and 0.1 mmol/L Pb/0.1 mmol/L ethylenediaminetetraacetic acid (EDTA) for 6 days. With the increasing Pb level, the Pb concentration in the shoots of AE plants enhanced accordingly, and EDTA supply helped 51% of Pb translocation to shoots of AE compared with those treated with 0.1 mmol/L Pb alone. Moreover, the presence of EDTA alleviated Pb phytotoxicity through changes in plant biomass, root morphology and chlorophyll contents. Lead toxicity induced hydrogen peroxide (H2O2) accumulation and lipid peroxidation in both ecotypes of S. alfredii. The activities of superoxide dismutase (SOD), guaiacol peroxidase (G-POD), ascorbate peroxidase, and dehydroascorbate reductase elevated in both leaves and roots of AE as well as in leaves of NAE with the increasing Pb levels, but SOD and G-POD declined in roots of NAE. Enhancement in glutathione reductase activity was only detected in roots of NAE while a depression in catalase activity was recorded in the leaves of NAE. A significant enhancement in glutathione and ascorbic acid (AsA)levels occurred in both ecotypes exposed to Pb and Pb/EDTA treatment compared with the control, however, the differences between these two treatments were insignificant. The dehydroascorbate (DHA) contents in roots of both ecotypes were 1.41 to 11.22-fold higher than those in leaves, whereas the ratios of AsA to DHA (1.38 to 6.84) in leaves altering more to the reduced AsA form were much higher than those in roots. These results suggested that antioxidative enzymes and antioxidants play an important role in counteracting Pb stress in S. alfredii.

Ultrastructural changes, zinc hyperaccumulation and its relation with antioxidants in two ecotypes of Sedum alfredii Hance.

Zn phytotoxicity and its possible detoxifying responses in two ecotypes of Sedum alfredii Hance, i.e. hyperaccumulating ecotype (HE) and non-hyperaccumulating ecotype (NHE) were investigated. HE grew better with high Zn concentrations of 29.11gkg(-1) DW in shoots when exposed to 500microM Zn2+. Toxicity symptoms caused by Zn in root cells of both ecotypes mainly included plasmolysis, disruption of plasma membranes and increased cell vacuolation. At high supplied Zn concentration, chloroplasts suffered from structural disorganization in both ecotypes. Zn-induced hydrogen peroxide (H2O2) and superoxide radical (O(2)-) productions in leaves were determined by a histochemical method, which revealed that Zn stress may have involved NADPH oxidase, protein phosphatases and intracellular Ca2+ to activate the reactive oxygen species production. Inhibition of glutathione synthesis may have led to increased H2O2 and O(2)- accumulations in leaves of HE. In response to higher Zn concentrations, ascorbic acid significantly increased in both ecotypes and levels of glutathione increased in both leaves and roots of HE and in roots of NHE without any change in the leaves of NHE. The enzymatic activities like those of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), guaiacol peroxidase (GPX, EC 1.11.1.7), ascorbate peroxidase (APX, EC 1.11.1.11), dehydroascorbate reductase (DHAR, EC 1.8.5.1), and glutathione reductase (GR, EC 1.6.4.2) in leaves of HE were all enhanced at supplied Zn concentration of 500microM, which may account for its better growth.

Heat stress protection in Aspen sp1 transgenic Arabidopsis thaliana.

It is known that the stable protein 1 (SP1) detected in aspen plants remains soluble upon boiling and that sp1 expression in transgenic aspen is resistant to salt stress. Presently, we analyzed the effect of expression of SP1 in Arabidopsis thaliana plants and their response to high temperature stress. After 45 degrees C for 16 h, relative to wild type plants, sp1 transgenic plants exhibited stronger growth and were better in several physiological properties including chlorophyll, chlorophyll fluorescence, water content, proline content, and malondialdehyde content. These preliminarily results suggest that the over-expression of SP1 may notably enhance heat-tolerant level of transgenic A. thaliana plants.

Influence of EDTA on lead transportation and accumulation by Sedum alfredii hance.

Hydroponics and pot experiments were conducted to study the effects of ethylenediaminetetraacetic acid (EDTA) on Pb transportation and accumulation by two contrasting ecotypes of Sedum alfredii Hance. In hydroponics experiments, the accumulating ecotype (AE) showed more ability to tolerate Pb toxicity compared with the non-accumulating ecotype (NAE). When treated with equimolar mixtures of EDTA and Pb, maximum Pb accumulation occurred without any phytotoxicity symptoms. Pot experiments with Pb contents of 400 mg kg-1 showed that 5 mM EDTA is the optimum dose for the phytoextraction of soils contaminated with relatively low Pb levels; in contrast, increasing EDTA addition resulted in increased Pb accumulation in the shoots of AE in soils with high Pb content (1200 mg kg(-1)). The post-harvest effects of EDTA on available Pb were strong compared with those without addition of EDTA (CK). Within the initial 7 days almost no differences of water-soluble Pb were noted in soils contaminated with both levels of Pb but after 2 weeks, water-soluble Pb started to decrease significantly compared with before. Considering the toxicity and biodegradability of synthetic chelators, it can be concluded that the chelate-assisted technique is more suitable for soils contaminated with low Pb levels and to avoid environment risks; a suitable dose of chelators must be considered before application.

Root responses and metal accumulation in two contrasting ecotypes of Sedum alfredii Hance under lead and zinc toxic stress.

Sedum alfredii Hance has been reported to be a Zn-hyperaccumulator plant species. In this study, root morphological and physiological response of the hyperaccumulating ecotype of S. alfredii H. (HE) from the mined area and the non-hyperaccumulating ecotype of S. alfredii H. (NHE) from the agricultural area to supplied levels of Zn and Pb were investigated. The results showed that Zn concentrations in the leaves and the stems of the HE were 34 and 41 times higher, whereas lead concentrations were 1.9 and 2.4 times greater, respectively, than those of the NHE when grown at 1224 microM Zn and/or 200 microM Pb. At combined supply of 1224 microM Zn with 200 microM Pb, however, zinc concentrations in the stems and leaves of the, HE decreased, while lead concentrations in the stems increased significantly, as compared with those of single metal treatment. Lead uptake of the HE was enhanced by Zn addition. Root activity of the HE decreased by Pb treatment in the first two days, but recovered afterward and close to the control at day 10 of the treatment. However, root activity of the NHE decreased by each metal treatment, and was not recovered with the advance of treatment time. Root length, root surface area, and root volumes increased obviously due to Zn and/or Pb/Zn combined treatments for the HE, but significantly decreased due to Pb, Zn, or Pb/Zn combined treatment for the NHE. Zinc and Pb concentrations in both ecotypes of S. alfredii H. were positively correlated with root length, root surface area, and root volumes. Root exudates of the HE, especially treated with Zn, increased the extractability of Pb and Zn from the mined soil. At the Zn supply level of 1224microM, the extractability of root exudates on soil Pb was 3-12 times greater for the HE than for the NHE. These results imply that the tolerance and hyperaccumulation of the hyperaccumulating ecotype of S. alfredii H. to Zn and Pb appear to be closely related to its high adaptation of root growth, morphology, and physiology to Pb and Zn toxicity, and through its root excretion of some special substances that can activate Pb and Zn in the mined soil, thus increasing their mobilization and bioavailability.